Compositions comprising nucleic acids encoding structural trimers and methods of using the same

ABSTRACT

Disclosed are compositions comprising an expressible nucleic acid sequence comprising a first nucleic acid sequence comprising a leader sequence or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence comprising a sequence that encodes a trimer of a retroviral envelope or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence further comprises a nucleic acid sequence encoding at least one viral antigen or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence further comprises at least one nucleic acid sequence encoding a linker. Also disclosed are pharmaceutical compositions comprising these compositions and methods of using the disclosed compositions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 62/829,629 filed on Apr. 4, 2019, which is incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

The embodiments disclosed herein were made with government support under U19 A1109646-04 awarded by the National Institutes of Health. The government has certain rights in the embodiments.

BACKGROUND

Despite extensive research and efforts, an efficacious HIV vaccine still eludes scientists. Two hurdles in HIV-1 vaccine development include the diversity of the HIV surface protein, Envelope, as well as the structure of this protein [1, 2]. Many vaccines have included subunits of Env which have generated significant binding antibodies but lack any effector functions, specifically neutralizing the HIV-1 virus [3, 4]. Recent advances in structural engineering and imaging have allowed for the development of a very limited number of properly folded native like HIV trimers [5-7]. However these are slow to develop and exceptionally costly to move to clinical testing. Furthermore, only a small number have been tested due to these issues and even the functional trimers lack the breadth necessary for broad protection against HIV. A new method for developing such complicated molecules directly in vivo would be game changing for this approach and would allow simple complex formulations that can be delivered as groups and provide broader immune protection. In addition, current recombinant methods for Trimer protein development cannot induce CD8 T cells but are limited to the induction of CD4 T helper responses, as well as antibody responses. Therefore, the current method lacks a critical immune component thought to be important for protection from HIV infection as well as for viral clearance. Presented herein is a demonstration that by designing synthetic DNA's that can fold in vivo to give complex structures native like trimers can be produced that yield improved T cell and antibody responses directly in living mammals, thus greatly advancing the vaccine field.

Through protein engineering in the laboratory there have been various forms of stabilized native like trimers which incorporate different amino acid mutations, modifications and truncations which allow for the proper folding and production of these trimers [6, 8][6, 8-11]. However, these proteins can be difficult to produce and purify, leading to lengthy manufacturing time and cost, which limits the application of this approach and in fact makes it a daunting challenge as a vaccine approach [12, 13]. Technologies that would allow de novo trimer formation in the host could potentially surpass the synthesis and purification steps required of recombinant trimer production. This would facility the rapid translation and iteration of various HIV-1 Env trimer strains both pre-clinically and in the clinic allowing for more diverse and protective collections of immunogens with improved deliverability. With the recent significant improvement in immunogenicity, the induction of potent specific humoral responses in animals and in the clinic, coupled with improved designs for complex synthetic molecule that require folding in vivo, the synthetic DNA vaccination platform represents an important tool for next generation design of viral antigens where in vivo folding of their antigens are important for immune function. Importantly, the work in the plasmid encoded synthetic DNA space has recently improved its ability to encode highly complex folded structures in vivo and have been described as highly functional and potent synthetic DNA encoded monoclonal antibodies launched directly in vivo [19-24].

SUMMARY OF EMBODIMENTS

Described herein is an in vivo molecule self-assembly for, in this case, HIV Envelope trimers through the use of advanced synthetic nucleic acid electroporation technology to rapidly design, encode, fold, express and or secrete various forms of HIV-1 native like trimers including long designed forms in vivo. Synthetic DNA encoded trimers can fold tightly and assume relevant conformations important for maintaining Envelope shape in vivo. These in vivo produced immunogens serve to induce autologous neutralizing antibodies and strong antigen specific T cell responses with robust CD4 helper responses in small animal models. This combination has not been previously achievable in a single platform. These responses can be further tailored to express novel trimer structures to focus the immune response in important ways by encoding modifications to the DNA sequence on the nucleotide level resulting in a final molecule that assembles in vivo capable of preventing or eliminating non-desired off-target antibody responses. This translates to many advantages for vaccine development including the ability to quickly produce or modify functional HIV Env trimers using simple DNA plasmids that allow for enhanced vaccine designs including for complex mixtures of trimers. These can be simply formatted as DNA as stable vaccine formulations in a simple, rapid deliverable and cost saving form for product development.

There are significant limitations in administering therapeutically effective amounts of protein vaccines to subjects, including ensuring that appropriate levels of the vaccine become exposed to antigen presenting cells and that the magnitude of any immune response is sufficient after administration of a single bolus dose. Furthermore, protein vaccines are difficult to store for relatively long periods of time because of protein instability issues. Synthetic designed DNA as immunogens represents an alternative vaccination technique that initially was limited in potency due to poor in vivo delivery and uptake. Encapsulation in compounds of older DNA was studied in the area of gene therapy and gene delivery but is expensive due to high doses needed, and poorly expressing, resulting in weak immunity and no functional immunity in vivo. To date, such approaches have not been reported to allow for reproducible complex molecule assembly in vivo for either biologic or vaccine production. Improved delivery technologies for synthetic DNA delivery is important in this regard.

To address these additional limitations and the limitations associated with biologic manufacturing of viral nanoparticles, the present disclosure relates to designing optimized nucleic acid sequences that can encode naturally self-assembling nanoparticles, that are not dependent on chemical formulations, as well as designed large antigen fragments and compositions comprising the same. In some embodiments, the disclosure relates to compositions comprising an expressible nucleic acid sequence comprising a first nucleic acid sequence comprising a leader sequence or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence comprising a sequence that encodes a self-assembling polypeptide or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence further encodes a third nucleic acid sequence that is a viral antigen. When the nucleic acid sequence is adminstered to a subject in the context of a method of treatment or prevention of the viral infection, antigen presenting cells can be transduced or transfected with the nucleic acid sequences disclosed herein to produce conformationally stable trimer polypeptides of pathogenic virus that more adequately elicit antigen-specific immune responses against the virus.

Disclosed are compositions comprising a nucleic acid sequence comprising at least one expressible nucleic acid sequence. In some embodiments, the composition comprises at least one, two, three, or more expressible nucleic acid sequences, wherein at least one of the expressible nucleic acid sequence comprises:

-   -   (i) one or a combination of nucleic acid sequences chosen from:         SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 57. SEQ         ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID         NO: 78. SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO:         84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 90,         SEQ ID NO: 91, SEQ ID NO:106, 107 SEQ ID NO: 109, SEQ ID NO:         110, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO:         116, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 121, SEQ ID NO:         122, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO:         128, SEQ ID NO: 130, SEQ ID NO: 131; and/or     -   (ii) one or a combination of nucleic acid sequences wherein the         at least one nucleic acid sequence comprises at least 70%         sequence identity to a sequence identified as including: AD8,         CPG9.2, 001428, TRO11, X2278, 398F1, 246F3, CE0217, CE1176,         25710, BJOX2000, CHI19, X1632, CNE8, CNE55, or 001428; and/or     -   (iii) one or a combination of nucleic acid sequences that encode         an amino acid sequence chosen from: SEQ ID NO: 55, SEQ ID NO:         58, SEQ ID NO: 61, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51,         SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 64, SEQ ID NO: 80, SEQ         ID NO: 83, SEQ ID NO: 86, SEQ ID NO:89, SEQ ID NO: 92, SEQ ID         NO: 93, SEQ ID NO: 94, SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID         NO: 114, SEQ ID NO: 117, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID         NO: 93, SEQ ID NO: 126, SEQ ID NO: 129, SEQ ID NO: 132; and/or     -   (iv) one or a combination of nucleic acid sequences that encode         at least one amino acid sequences comprising at least 70%         sequence identity to a sequence identified as including: AD8,         CPG9.2, 001428, TRO11, X2278, 398F1, 246F3, CE0217, CE1176,         25710, BJOX2000, CHI19, X1632, CNE8, CNE55, or 001428. Disclosed         are compositions comprising an expressible nucleic acid sequence         comprising a first nucleic acid sequence comprising a soluble         retroviral trimer or a pharmaceutically acceptable salt thereof.

Disclosed are compositions comprising an expressible nucleic acid sequence comprising: a first nucleic acid sequence comprising at least 70% sequence identity to a nucleotide sequence encoding a soluble polypeptide monomer of or trimer of human immunodeficiency virus-1 (HIV-1) ENV; and a regulatory sequence operably linked to the first nucleotide sequence. Disclosed are pharmaceutical compositions comprising any of the compositions disclosed herein and a pharmaceutically acceptable carrier. In some embodiments, if a monomer is encoded it is a monomer capable of forming a trimer upon expression within a cell. In some embodiments, the expressible nucleic acid sequence further comprises a nucleic acid sequence encoding at least one viral antigen or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence further comprises at least one nucleic acid sequence encoding a linker. The disclosure also relates to pharmaceutical compositions comprising any one or more of the disclosed compositions and a pharmaceutically acceptable carrier.

Disclosed are methods of vaccinating a subject comprising administering a therapeutically effective amount of any of the disclosed pharmaceutical compositions to the subject. The disclosure relates to methods of inducing an immune response in a subject comprising administering to the subject any of the disclosed pharmaceutical compositions.

Disclosed are methods of neutralizing one or a plurality of viruses in a subject comprising administering to the subject any of the disclosed pharmaceutical compositions.

Disclosed are methods of stimulating a therapeutically effective antigen-specific immune response against a virus in a mammal infected with the virus comprising administering any of the disclosed pharmaceutical compositions. Disclosed are methods of inducing expression of a self-assembling vaccine in a subject comprising administering any of the disclosed pharmaceutical compositions.

Disclosed are vaccines comprising a first amino acid sequence comprising at least 70% sequence identity to a leader sequence; and/or a second amino acid sequence comprising at least 70% sequence identity to a linker sequence.

Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.

Disclosed are methods of immunizing a subject in need thereof comprising administering a therapeutically effective amount of any of the disclosed pharmaceutical compositions to the subject. In some embodiments, the immunization is induced against HIV infection.

Also disclosed are methods of eliciting an antigen-specific immune response against a trimer in a subject in need thereof comprising administering a therapeutically effective amount of any of the disclosed pharmaceutical compositions to the subject. In some embodiments, the trimer is an HIV trimer.

In some embodiments, the administering in the disclosed methods is accomplished by oral administration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof. In some embodiments, the therapeutically effective dose in the disclosed methods is from about 1 to about 30 micrograms of expressible nucleic acid sequence. In some embodiments, the methods are free of activating any mannose-binding lectin or complement process. In some embodiments, the subject is a human. In some embodiments, the therapeutically effective dose in the disclosed methods is from about 0.001 micrograms of composition per kilogram of the subject to about 0.050 micrograms per kilogram of the subject. In some embodiments, any of the disclosed methods can be used in combination with retrovirals.

The disclosure relates to nucleic acid sequences that encode a retroviral antigen that are free of a transmembrane domain. In some embodiments, the retroviral antigen is the envelope glycoprotein gp120 of the HIV. In some embodiments, the retroviral antigen is free of the HIV-1 transmembrane domain gp41.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions.

FIGS. 1A, 1B, 1C, and 1D show DNA vs protein immunization and the superior T cell responses with DNA. A) schematic diagram of immunization schedule. Mice were immunized with 25 ug of pMD39-OPT DNA with IM EP-CELLECTRA 3P or 25 ug of protein MD39 formulated in RIBI and delivered to two sites SubQ. Each mouse received 3 immunizations at 3 week intervals. T cell responses were determined 2 weeks after final immunization using overlapping peptides for the WT BG505 Envelope virus sequence. B) IFNy ELISpots using BG505 WT Env peptides. DNA immunize mice have immune responses to the entire antigen. D) these T cell responses are to both CD4 and CD8 T cells. C & E) These T cells are polyfunctional and express multiple cytokines. DNA induces stronger T cell responses compared to protein using multiple different measures including IFN-y ELISpots and ICS. Both CD4 and CD8 were induced by DNA.

FIGS. 2A, 2B, 2C, and 2D show DNA vs protein immunization and similar binding titer responses. A) schematic diagram of immunization schedule. The dose used was 25 ug of pMD39-Opt; 25 ug of protein MD39; formulated in RIBI and delivered to two sites. B) The humoral responses for the mice were determined 2 weeks post each vaccinations. DNA is able to induce binding titers to trimeric HIV Env slightly higher than protein only immunizations. C) Post final immunization, there is not a significant difference between the two groups. D) It has been reported that mice cannot induce neutralizing titers to BG505 Tier 2 virus. However, using the same antigen, in rabbits and NHPs, autologous Tier 2, narrow neutralization titers were induced with protein. However, serum from mice immunized with DNA encoded trimers were able to induce autologous tier 2 neutralizing titers in 3 out of 10 mice. The serum was also tested against MLV to ensure there was not non-specific neutralization.

FIGS. 3A, 3B, 3C, 3D, and 3E show increasing the interval between immunizations improved cellular responses. A) schematic diagram of immunization schedule. Mice were immunized with 25 ug of pMD39_Opt DNA with IM-EP Cellectra 3P 3 times at either 0, 3, 6 or 0, 3, 16 weeks and euthanized the mice two weeks post final immunizations. B) IFNy ELISpots using BG505 WT Env peptides. Mice immunized at the longer interval had increase IFNy SFU. C) these T cell responses are to both CD4 and CD8 T cells. D & E) These T cells are polyfunctional and express multiple cytokines. The shorter immunization schedule induce better CD8 T cells where as the longer immunization had better CD4 T cell responses.

FIGS. 4A, 4B, 4C, 4D, and 4E shows increasing the interval between immunizations results in similar binding titers. A) schematic diagram of immunization schedule. 25 ug of plasmid DNA+IM-EP was used as the dose. B) and C) Binding to HIV Env Trimer over time. Observe good durability of antibody responses between the second and pre third immunizations. D) Binding antibodies to trimeric Env post final immunization. There is no difference in binding titers between the long vs short immunization schedule. E) Binding titers to monomers post final immunization—also similar between the two schedule.

FIGS. 5A, and 5B show increasing the interval between immunizations resulted in improved functional (neutralizing) antibodies. A) Even though binding titers were the same between the two groups, neutralization titers against autologous antibodies were stronger with the longer immunization. There were 7 out of 10 mice that induced autologous BG505 neutralization titers compared to 3 out of 10 with the short immunizations. B) The table shows the titers for each mouse as well as no neutralization with MLV.

FIGS. 6A, 6B, and 6C show similar trimer binding antibodies with soluble vs membrane bound trimers. All trimers were RNA and codon optimized and cloned into modified pVax 1 backbone with an IgE leader sequence added to the beginning of the construct. Modifications were made to the plasmid insert to tailor the vaccine induced responses A) schematic diagram of immunization schedule. Dosage is 25 ug of SynDNA+IM-EP CELLECTRA-3P; B) Trimer binding titer; C) GP120 monomer binding titer.

FIGS. 7A, 7B, and 7C show the strongest T cell responses are observed with soluble constructs. A) schematic diagram of immunization schedule. The dose is 25 ug of SynDNA+IM-EP CELLECTRA-3P. B) IFNy ELISpots using BG505 WT Env peptides. Mice immunized at the longer interval had increase IFNy SFU. C) these T cell responses are to both CD4 and CD8 T cells.

FIGS. 8A, 8B, and 8C show SynDNA trimers lower antibodies binding to V3 loop compared to controls. A) Full length V3; B) End V3; C) Tip V3. The exposure of these peptides decreases moving from A-C. There were no responses to scramble peptides. This supports that these antigens are being properly folded. DNA encoded structural immunogens decreases off target V3 binding antibody responses compared to GP120 foldon.

FIG. 9A show DNA encoded modifications limit bottom binding antibodies. A) Competition ELISA results using the bottom binding antibody 12N. On pMD39_opt the bottom of the trimer is exposed. Normally on the virus, this region is linked to the transmembrane domain and tethered to the virion. To prevent this exposure, glycans or linkers can be added. These modifications were tested to determine if they could decrease the bottom reactivity using a monoclonal that will bind to MD39 trimer (12N). Using a competition ELISA a significant decrease in the amount of antibodies that bind to the bottom of MD39 trimers with either glycans, linkers or forcing the antigen to be tethered to the membrane was observed. Different modifications can be encoded in DNA and can translate to in vivo immune responses. Additionally it is an indirect demonstration that glycan sites can be encoded and glycosylation events obtained.

FIG. 10 shows soluble SynDNA trimers induce better autologous (Tier 2) neutralizing antibody titers compared to other DNA encoded immunogens. The soluble antigens induce between 60-70% of autologous neutralizing antibody titers compared to 10-50% with the membrane bound antigens. There was no neutralization with MLV control virus. The graph represents a combination of two separate experiments.

FIGS. 11A, 11B show DNA induced NAb responses in mice do not target the 241/289 glycan hole but do target the T65n/C3 region of the Env. A) There is a monoclonal antibody which binds to the epitope which is dominant in rabbits immunized with a similar protein antigen, 11A. This antibody binds to a hole in the glycans on HIV Env at the 241 position. A competition ELISA was used to determine if the serum is binding to this epitope. Serum from mice immunized at wk 0, 3, 16 (wk 18 serum was used) for the competition with 11A. There was no competition with 11A from the mouse serum. B) To map where the serum was neutralizing, pseudotype viruses with various point mutations of known neutralization regions were used. Two groups of serum were used, those neutralizing BG505 autologous viruses (neutralizers) vs those that did not induce titers (non-neutralizers). There was no change in neutralization titers when the S241N mutations was made to the virus but here was a significant drop in neutralization when the T465N mutation was made. Thus, neutralizing antibodies are binding to the T465/C3 region of BG505. Furthermore, the maternal strain (MG505) which was the transmitting virus into the baby girl (BG505) for which this initial Env sequence was isolated, is closely related (17AA differences). One of these is in the region previously observed in NHPs (1396N). This could explain why MG505 is not neutralized by the mouse serum. MLV shown as a control.

FIG. 12A, 12B, 12C shows a rabbit study with SynDNA SOSIP Trimers immunizations. A) Diagramed of rabbit immunization schedule. Four different immunogens into rabbits, pOpt MD39, pOpt MD39_Glycan, pOpt_TS1, pOpt_TS1_PDGFR. Rabbits were immunized with either 1-2 mg of DNA based on the molar amount delivered to two sites ID with CELLECTRA 3P. Rabbits were immunized at week 0, 4, 12, 20. B) Binding to trimer over time; C) Binding to trimer week 14 (post 3^(rd) boost). Trimer specific antibody responses were detected with complete seroconversion post second immunization. These responses were slightly higher with MD39 compared to the other DNA encoded immunogens.

FIG. 13 shows an example of early titers against autologous BG505 T332N virus—First Tier 2 Neuts with SynDNA alone. Some neutralization titers were observed post third immunization against autologous viruses with boost following the forth immunization. There was limited to no non-specific neutralizing titers.

FIGS. 14A, 14B, and 14C shows a immunogenicity of selected synDNA trimers in a larger animal, non-human primate. A) Diagram of immunizations. NHPS (non-human primates) were immunized with 2 mgs of DNA delivered to two sites ID with CELLECTRA 3P. NHPS were immunized at weeks 0, 4, 12, and 20 with either pOpt MD39_Glycan or pOpt TS_1. B) IFNy ELISpots over time after stimulation with WT BG505 overlapping peptides. B) Week 14 individual NHPs. T cells responses were observed over background post 1 dose which are further expanded post dose 2 and 3. Most NHPS are responses to all parts of the antigen at week 6 and expand by week 14.

FIGS. 15A, 15B and 15C show humoral responses induced in NHP over time with synDNA encoded trimer immunogens. A) Trimer binding antibodies over time. Complete seroconversion is observed after the 2^(nd) dose. B) Binding titers to gp120 monomer over time. C) Comparison between the two groups binding titers to trimer vs gp120 monomer at week 14.

DETAILED DESCRIPTION

The disclosed method and compositions may be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description.

It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.

It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to “a nucleic acid sequence” includes a plurality of such sequences, reference to “the nucleic acid sequence” is a reference to one or more nucleic acid sequences and equivalents thereof known to those skilled in the art, and so forth.

As used herein, the terms “activate,” “stimulate,” “enhance” “increase” and/or “induce” (and like terms) are used interchangeably to generally refer to the act of improving or increasing, either directly or indirectly, a concentration, level, function, activity, or behavior relative to the natural, expected, or average, or relative to a control condition. “Activate” in context of an immunotherapy refers to a primary response induced by ligation of a cell surface moiety. For example, in the context of receptors, such stimulation entails the ligation of a receptor and a subsequent signal transduction event. Further, the stimulation event may activate a cell and upregulate or downregulate expression or secretion of a molecule. Thus, indirect or direct ligation of cell surface moieties, even in the absence of a direct signal transduction event, may result in the reorganization of cytoskeletal structures, or in the coalescing of cell surface moieties, each of which could serve to enhance, modify, or alter subsequent cellular responses. As used herein, the terms “activating CD8+ T cells” or “CD8+ T cell activation” refer to a process (e.g., a signaling event) causing or resulting in one or more cellular responses of a CD8+ T cell (CTL), selected from: proliferation, differentiation, cytokine secretion, cytotoxic effector molecule release, cytotoxic activity, and expression of activation markers. As used herein, an “activated CD8+ T cell” refers to a CD8+ T cell that has received an activating signal, and thus demonstrates one or more cellular responses, selected from proliferation, differentiation, cytokine secretion, cytotoxic effector molecule release, cytotoxic activity, and expression of activation markers. Suitable assays to measure CD8+ T cell activation are known in the art and are described herein.

The term “combination therapy” as used herein is meant to refer to administration of one or more therapeutic agents in a sequential manner, that is, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents, in a substantially simultaneous manner. Substantially simultaneous administration can be accomplished, for example, by administering to the subject a single dose having a fixed ratio of each therapeutic agent or in multiple, individual doses for each of the therapeutic agents. For example, one combination of the present invention may comprise a pooled sample of one or more nucleic acid molecules comprising one or a plurality of expressible nucleic acid sequences and an adjuvant and/or an anti-viral agent administered at the same or different times. In some embodiments, the pharmaceutical composition of the disclosure can be formulated as a single, co-formulated pharmaceutical composition comprising one or more nucleic acid molecules comprising one or a plurality of expressible nucleic acid sequences and one or more adjuvants and/or one or more anti-viral agents. As another example, a combination of the present disclosure (e.g., DNA vaccines and anti-viral agent) may be formulated as separate pharmaceutical compositions that can be administered at the same or different time. As used herein, the term “simultaneously” is meant to refer to administration of one or more agents at the same time. For example, in certain embodiments, antiviral vaccine or immunogenic composition and antiviral agents are administered simultaneously). Simultaneously includes administration contemporaneously, that is during the same period of time. In certain embodiments, the one or more agents are administered simultaneously in the same hour, or simultaneously in the same day. Sequential or substantially simultaneous administration of each therapeutic agent can be effected by any appropriate route including, but not limited to, oral routes, intravenous routes, subcutaneous routes, intramuscular routes, direct absorption through mucous membrane tissues (e.g., nasal, mouth, vaginal, and rectal), and ocular routes (e.g., intravitreal, intraocular, etc.). The therapeutic agents can be administered by the same route or by different routes. For example, one component of a particular combination may be administered by intravenous injection while the other component(s) of the combination may be administered intramuscularly only. The components may be administered in any therapeutically effective sequence. A “combination” embraces groups of compounds or non-small chemical compound therapies useful as part of a combination therapy.

As used herein, “expression” refers to the process by which a polynucleotide is transcribed from a DNA template (such as into and mRNA or other RNA transcript) and/or the process by which a transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins. Transcripts and encoded polypeptides may be collectively referred to as “gene product.” If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

The terms “functional fragment” means any portion of a polypeptide or nucleic acid sequence from which the respective full-length polypeptide or nucleic acid relates that is of a sufficient length and has a sufficient structure to confer a biological affect that is at least similar or substantially similar to the full-length polypeptide or nucleic acid upon which the fragment is based. In some embodiments, a functional fragment is a portion of a full-length or wild-type nucleic acid sequence that encodes any one of the nucleic acid sequences disclosed herein, and said portion encodes a polypeptide of a certain length and/or structure that is less than full-length but encodes a domain that still biologically functional as compared to the full-length or wild-type protein. In some embodiments, the functional fragment may have a reduced biological activity, about equivalent biological activity, or an enhanced biological activity as compared to the wild-type or full-length polypeptide sequence upon which the fragment is based. In some embodiments, the functional fragment is derived from the sequence of an organism, such as a human. In such embodiments, the functional fragment may retain about 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or 90% sequence identity to the wild-type human sequence upon which the sequence is derived. In some embodiments, the functional fragment may retain about 85%, 80%, 75%, 70%, 65%, or 60% sequence identity to the wild-type sequence upon which the sequence is derived. By “fragment” is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, preferably, at least about about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or about 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain about 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 or more nucleotides or amino acids.

“Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and/or B,” when used in conjunction with open-ended language such as “comprising” can refer, in some embodiments, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

As used herein in the specification and in the claims, “or” should he understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

As used herein an “antigen” is meant to refer to any substance that elicits an immune response.

As used herein, the term “electroporation,” “electro-permeabilization,” or “electro-kinetic enhancement” (“EP”), are used interchangeably and are meant to refer to the use of a transmembrane electric field pulse to induce microscopic pathways (pores) in a bio-membrane; their presence allows biomolecules such as plasmids, oligonucleotides, siRNA, drugs, ions, and/or water to pass from one side of the cellular membrane to the other. In some of the disclosed methods of treatment or prevention, the method comprises a step of electroporation of a subject's tissue for a sufficient time and with a sufficient electrical field capable of inducing uptake of the pharmaceutical compositions disclosed herein into the antigen-presenting cells. In some embodiments, the cells are antigen presenting cells.

The term “pharmaceutically acceptable excipient, carrier or diluent” as used herein is meant to refer to an excipient, carrier or diluent that can be administered to a subject, together with an agent, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent. The term “pharmaceutically acceptable salt” of nucleic acids as used herein may be an acid or base salt that is generally considered in the art to be suitable for use in contact with the tissues of human beings or animals without excessive toxicity, irritation, allergic response, or other problem or complication. Such salts include mineral and organic acid salts of basic residues such as amines, as well as alkali or organic salts of acidic residues such as carboxylic acids. Specific pharmaceutical salts include, but are not limited to, salts of acids such as hydrochloric, phosphoric, hydrobromic, malic, glycolic, fumaric, sulfuric, sulfamic, suifanilic, formic, toluenesulfonie, methanesulfonic, benzene sulfonic, ethane disulfonic, 2-hydroxyethyl sulfonic, nitric, benzoic, 2-acetoxybenzoic, citric, tartaric, lactic, stearic, salicylic, glutamic, ascorbic, pamoic, succinic, fumaric, maleic, propionic, hydroxymaleic, hydroiodic, phenyiacetic, alkanoic such as acetic, HOOC—(CH₂)n-COOH where n is 0-4, and the like. Similarly, pharmaceutically acceptable cations include, but are not limited to sodium, potassium, calcium, aluminum, lithium and ammonium. Those of ordinary skill in the art will recognize from this disclosure and the knowledge in the art that further pharmaceutically acceptable salts for the pooled viral specific antigens or polynucleotides provided herein, including those listed by Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., p. 1418 (1985). In general, a pharmaceutically acceptable acid or base salt can be synthesized from a parent compound that contains a basic or acidic moiety by any conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in an appropriate solvent.

As used herein, the terms “prevent,” “preventing,” “prevention,” “prophylactic treatment,” and the like, are meant to refer to reducing the probability of developing a disease or condition in a subject, who does not have, but is at risk of or susceptible to developing a disease or condition.

As used herein, the term “purified” means that the polynucleotide or polypeptide or fragment, variant, or derivative thereof is substantially free of other biological material with which it is naturally associated, or free from other biological materials derived, e.g., from a recombinant host cell that has been genetically engineered to express the polypeptide of the invention. That is, e.g., a purified polypeptide of the present disclosure is a polypeptide that is at least from about 70% to about 100% pure, i.e., the polypeptide is present in a composition wherein the polypeptide constitutes from about 70% to about 100% by weight of the total composition. In some embodiments, the purified polypeptide of the present disclosure is from about 75% to about 99% by weight pure, from about 80% to about 99% by weight pure, from about 90 to about 99% by weight pure, or from about 95% to about 99% by weight pure.

The terms ““subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, cows, pigs, goats, sheep, horses, dogs, sport animals, and pets. Tissues, cells and their progeny obtained in vivo or cultured in vitro are also encompassed by the definition of the term “subject.” The term “subject” is also used throughout the specification in some embodiments to describe an animal from which a cell sample is taken or an animal to which a disclosed cell or nucleic acid sequences have been administered. In some embodiment, the subject is a human. For treatment of those conditions which are specific for a specific subject, such as a human being, the term “patient” may be interchangeably used. In some instances in the description of the present disclosure, the term “patient” will refer to human patients suffering from a particular disease or disorder. In some embodiments, the subject may be a non-human animal. The term “mammal” encompasses both humans and non-humans and includes but is not limited to humans, non-human primates, canines, felines, murines, bovines, equines, caprines, and porcines.

The term “therapeutic effect” as used herein is meant to refer to some extent of relief of one or more of the symptoms of a disorder (e.g., HIV infection) or its associated pathology. A “therapeutically effective amount” as used herein is meant to refer to an amount of an agent which is effective, upon single or multiple dose administration to the cell or subject, in prolonging the survivability of the patient with such a disorder, reducing one or more signs or symptoms of the disorder, preventing or delaying, and the like beyond that expected in the absence of such treatment. A “therapeutically effective amount” is intended to qualify the amount required to achieve a therapeutic effect. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the “therapeutically effective amount” (e.g., ED50) of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds of the invention employed in a pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

The terms “treat,” “treated,” “treating,” “treatment” and the like as used herein are meant to refer to reducing or ameliorating a disorder and/or symptoms associated therewith (e.g., a HIV or AIDS). “Treating” may refer to administration of the DNA vaccines described herein to a subject after the onset, or suspected onset, of a viral infection. “Treating” includes the concepts of “alleviating,” which refers to lessening the frequency of occurrence or recurrence, or the severity, of any symptoms or other ill effects related to a HIV and/or the side effects associated with viral infection. The term “treating” also encompasses the concept of “managing” which refers to reducing the severity of a particular disease or disorder in a patient or delaying its recurrence, e.g., lengthening the period of remission in a patient who had suffered from the disease. It is appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition, or symptoms associated therewith be completely eliminated.

For any therapeutic agent described herein the therapeutically effective amount may be initially determined from preliminary in vitro studies and/or animal models. A therapeutically effective dose may also be determined from human data. The applied dose may be adjusted based on the relative bioavailability and potency of the administered agent adjusting the dose to achieve maximal efficacy based on the methods described above and other well-known methods is within the capabilities of the ordinarily skilled artisan. General principles for determining therapeutic effectiveness, which may be found in Chapter 1 of Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th Edition, McGraw-Hill (New York) (2001), incorporated herein by reference, are summarized below. Pharmacokinetic principles provide a basis for modifying a dosage regimen to obtain a desired degree of therapeutic efficacy with a minimum of unacceptable adverse effects. In situations where the drug's plasma concentration can be measured and related to the therapeutic window, additional guidance for dosage modification can be obtained. Drug products are considered to be pharmaceutical equivalents if they contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration. Two pharmaceutically equivalent drug products are considered to be bioequivalent when the rates and extents of bioavailability of the active ingredient in the two products are not significantly different under suitable test conditions.

The terms “polynucleotide,” “oligonucleotide” and “nucleic acid” are used interchangeably throughout and include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs (e.g., peptide nucleic acids and non-naturally occurring nucleotide analogs), and hybrids thereof. The nucleic acid molecule can be single-stranded or double-stranded. In some embodiments, the nucleic acid molecules of the disclosure comprise a contiguous open reading frame encoding an antibody, or a fragment thereof, as described herein. “Nucleic acid” or “oligonucleotide” or “polynucleotide” as used herein may mean at least two nucleotides covalently linked together. The depiction of a single strand also defines the sequence of the complementary strand. Thus, a nucleic acid also encompasses the complementary strand of a depicted single strand. Many variants of a nucleic acid may be used for the same purpose as a given nucleic acid. Thus, a nucleic acid also encompasses substantially identical nucleic acids and complements thereof. A single strand provides a probe that may hybridize to a target sequence under stringent hybridization conditions. Thus, a nucleic acid also encompasses a probe that hybridizes under stringent hybridization conditions. Nucleic acids may be single stranded or double stranded, or may contain portions of both double stranded and single stranded sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine and isoguanine. Nucleic acids may be obtained by chemical synthesis methods or by recombinant methods. A nucleic acid will generally contain phosphodiester bonds, although nucleic acid analogs maybe included that may have at least one different linkage, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or 0-methylphosphoroamidite linkages and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, which are incorporated by reference in their entireties.

Nucleic acids containing one or more non-naturally occurring or modified nucleotides are also included within one definition of nucleic acids. The modified nucleotide analog may he located for example at the 5′-end and/or the 3′-end of the nucleic acid molecule. Representative examples of nucleotide analogs may be selected from sugar- or backbone-modified ribonucleotides. It should be noted, however, that also nucleobase-modified ribonucleotides, i.e. ribonucleotides, containing a non-naturally occurring nucleobase instead of a naturally occurring nucleobase such as uridines or cytidines modified at the 5-position, e.g. 5-(2-amino)propyl uridine, 5-bromo uridine; adenosines and guanosines modified at the 8-position, e.g. 8-bromo guanosine; deaza nucleotides, e.g. 7-deaza-adenosine; 0- and N-alkylated nucleotides, e.g. N6-methyl adenosine are suitable. The 2′-OH-group may be replaced by a group selected from H, OR, R, halo, SH, SR, NH₂, NHR, N₂ or CN, wherein R is C₁-C₆ alkyl, alkenyl or alkynyl and halo is F, Cl, Br or I. Modified nucleotides also include nucleotides conjugated with cholesterol through, e.g., a hydroxyprolinol linkage as described in Krutzfeldt et al., Nature (Oct. 30, 2005), Soutschek et al., Nature 432:173-178 (2004), and U.S. Patent Publication No. 20050107325, which are incorporated herein by reference in their entireties. Modified nucleotides and nucleic acids may also include locked nucleic acids (LNA), as described in U.S. Patent No. 20020115080, which is incorporated herein by reference. Additional modified nucleotides and nucleic acids are described in U.S. Patent Publication No. 20050182005, which is incorporated herein by reference in its entirety. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments, to enhance diffusion across cell membranes, or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs may be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. In some embodiments, the expressible nucleic acid sequence is in the form of DNA. In some embodiments, the expressible nucleic acid is in the form of RNA with a sequence that encodes the polypeptide sequences disclosed herein and, in some embodiments, the expressible nucleic acid sequence is an RNA/DNA hybrid molecule that encodes any one or plurality of polypeptide sequences disclosed herein.

As used herein, the term “nucleic acid molecule” is a molecule that comprises one or more nucleotide sequences that encode one or more proteins. In some embodiments, a nucleic acid molecule comprises initiation and termination signals operably linked to regulatory elements including a promoter and polyadenylation signal capable of directing expression in the cells of the individual to whom the nucleic acid molecule is administered. In some embodiments, the nucleic acid molecule also includes a plasmid containing one or more nucleotide sequences that encode one or a plurality of viral antigens. In some embodiments, the disclosure relates to a pharmaceutical composition comprising a first, second, third or more nucleic acid molecule, each of which encoding one or a plurality of viral antigens and at least one of each plasmid comprising one or more of the compositions disclosed herein.

The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-natural amino acids or chemical groups that are not amino acids. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. As used herein the term “amino acid” includes natural and/or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics.

The “percent identity” or “percent homology” of two polynucleotide or two polypeptide sequences is determined by comparing the sequences using the GAP computer program (a part of the GCG Wisconsin Package, version 10.3 (Accelrys, San Diego, Calif.)) using its default parameters. “Identical” or “identity,” as used herein in the context of two or more nucleic acids or amino acid sequences, may mean that the sequences have a specified percentage of residues that are the same over a specified region. The percentage may be calculated by optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces one or more staggered ends and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) may be considered equivalent. Identity may he performed manually or by using a computer sequence algorithm such as BLAST or BLAST 2.0. Briefly, the BLAST algorithm, which stands for Basic Local Alignment Search Tool is suitable for determining sequence similarity. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). This algorithm involves first identifying high scoring sequence pair (HSPs) by identifying short words of length Win the query sequence that either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Extension for the word hits in each direction are halted when: 1) the cumulative alignment score falls off by the quantity X from its maximum achieved value; 2) the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or 3) the end of either sequence is reached. The Blast algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The Blast program uses as defaults a word length (W) of 11, the BLOSUM62 scoring matrix (see Henikoff et al., Proc. Natl. Acad. Sci. USA, 1992, 89, 10915-10919, which is incorporated herein by reference in its entirety) alignments (B) of 50, expectation (E) of 10, M=5, N=4, and a comparison of both strands. The BLAST algorithm (Karlin et al., Proc. Natl. Acad. Sci. USA, 1993, 90, 5873-5787, which is incorporated herein by reference in its entirety) and Gapped BLAST perform a statistical analysis of the similarity between two sequences. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide sequences would occur by chance. For example, a nucleic acid is considered similar to another if the smallest sum probability in comparison of the test nucleic acid to the other nucleic acid is less than about 1, less than about 0.1, less than about 0.01, and less than about 0.001. Two single-stranded polynucleotides are “the complement” of each other if their sequences can be aligned in an anti-parallel orientation such that every nucleotide in one polynucleotide is opposite its complementary nucleotide in the other polynucleotide, without the introduction of gaps, and without unpaired nucleotides at the 5′ or the 3′ end of either sequence. A polynucleotide is “complementary” to another polynucleotide if the two polynucleotides can hybridize to one another under moderately stringent conditions. Thus, a polynucleotide can be complementary to another polynucleotide without being its complement.

By “substantially identical” is meant nucleic acid molecule (or polypeptide) exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least about 60%, 70%, 80% or 85%, 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison.

A nucleotide sequence is “operably linked” to a regulatory sequence if the regulatory sequence affects the expression (e.g., the level, timing, or location of expression) of the nucleotide sequence. A “regulatory sequence” is a nucleic acid that affects the expression (e.g., the level, timing, or location of expression) of a nucleic acid to which it is operably linked. The regulatory sequence can, for example, exert its effects directly on the regulated nucleic acid, or through the action of one or more other molecules (e.g., polypeptides that bind to the regulatory sequence and/or the nucleic acid). Examples of regulatory sequences include promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Further examples of regulatory sequences are described in, for example, Goeddel, 1990, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. and Baron et al., 1995, Nucleic Acids Res. 23:3605-06.

A “vector” is a nucleic acid that can be used to introduce another nucleic acid linked to it into a cell. One type of vector is a “plasmid,” which refers to a linear or circular double stranded DNA molecule into which additional nucleic acid segments can be ligated. Another type of vector is a viral vector (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), wherein additional DNA segments can be introduced into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors comprising a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. An “expression vector” is a type of vector that can direct the expression of a chosen polynucleotide. The disclosure relates to any one or plurality of vectors that comprise nucleic acid sequences encoding any one or plurality of amino acid sequence disclosed herein.

The term “vaccine” as used herein is meant to refer to a composition for generating immunity for the prophylaxis and/or treatment of diseases (e.g., viral infections). Accordingly, vaccines are medicaments which comprise antigens in protein and/or nucleic acid forms and are intended to be used in humans or animals for generating specific defense and protective substance by vaccination. A “vaccine composition” or a “DNA vaccine composition” can include a pharmaceutically acceptable excipient, earner or diluent.

Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and/or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, +10%, ±5%, ±1%, ±0.5%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

“Variants” is intended to mean substantially similar sequences. For nucleic acid molecules, a variant comprises a nucleic acid molecule having deletions (i.e., truncations) at the 5′ and/or 3′ end; deletion and/or addition of one or more nucleotides at one or more internal sites in the native polynucleotide; and/or substitution of one or more nucleotides at one or more sites in the native polynucleotide. As used herein, a “native” nucleic acid molecule or polypeptide comprises a naturally occurring nucleotide sequence or amino acid sequence, respectively. For nucleic acid molecules, conservative variants include those sequences that, because of the degeneracy of the genetic code, encode the amino acid sequence of one of the polypeptides of the disclosure. Variant nucleic acid molecules also include synthetically derived nucleic acid molecules, such as those generated, for example, by using site-directed mutagenesis but which still encode a protein of the disclosure. Generally, variants of a particular nucleic acid molecule of the disclosure will have at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to that particular polynucleotide as determined by sequence alignment programs and parameters as described elsewhere herein. Variants of a particular nucleic acid molecule of the disclosure (i.e., the reference DNA sequence) can also be evaluated by comparison of the percent sequence identity between the polypeptide encoded by a variant nucleic acid molecule and the polypeptide encoded by the reference nucleic acid molecule. Percent sequence identity between any two polypeptides can be calculated using sequence alignment programs and parameters described elsewhere herein. Where any given pair of nucleic acid molecule of the disclosure is evaluated by comparison of the percent sequence identity shared by the two polypeptides that they encode, the percent sequence identity between the two encoded polypeptides is at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity. In some embodiments, the term “variant” protein is intended to mean a protein derived from the native protein by deletion (so-called truncation) of one or more amino acids at the N-terminal and/or C-terminal end of the native protein; deletion and/or addition of one or more amino acids at one or more internal sites in the native protein; or substitution of one or more amino acids at one or more sites in the native protein. Variant proteins encompassed by the present disclosure are biologically active, that is they continue to possess the desired biological activity of the native protein as described herein. Such variants may result from, for example, genetic polymorphism or from human manipulation. Biologically active variants of a protein of the disclosure will have at least about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to the amino acid sequence for the native protein as determined by sequence alignment programs and parameters described elsewhere herein. A biologically active variant of a protein of the disclosure may differ, in some embodiments, from that protein by as few as about 1 to about 15 amino acid residues, as few as about 1 to about 10, such as about 6-to about 10, as few as about 5, as few as 4, 3, 2, or even 1 amino acid residue. The proteins or polypeptides of the disclosure may be altered in various ways including amino acid substitutions, deletions, truncations, and insertions. Methods for such manipulations are generally known in the art. For example, amino acid sequence variants and fragments of the proteins can be prepared by mutations in the nucleic acid sequence that encode the amino acid sequence recombinantly. In some embodiments, the nucleic acid molecules or the nucleic acid sequences comprise conservative mutations of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleotides.

Finally, it should be understood that all of the individual values and sub-ranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these embodiments are explicitly disclosed.

Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as described. Publications cited herein and the material for which they are cited are hereby specifically incorporated by reference in their entireties. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinence of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.

Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. In particular, in methods stated as comprising one or more steps or operations it is specifically contemplated that each step comprises what is listed (unless that step includes a limiting term such as “consisting of”), meaning that each step is not intended to exclude, for example, other additives, components, integers or steps that are not listed in the step.

A. Nucleic Acid Compositions

Disclosed are compositions comprising an expressible nucleic acid sequence comprising a first nucleic acid sequence encoding a retroviral trimer polypeptide, a functional fragment thereof or a pharmaceutically acceptable salt thereof. In some embodiments, the disclosure relates to compositions comprising an expressible nucleic acid sequence comprising, in a 5′ to 3′ orientation, a first nucleic acid sequence comprising a leader sequence, functional fragment thereof or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence encoding a retroviral trimer polypeptide, a functional fragment thereof or a pharmaceutically acceptable salt thereof. In some embodiments, the disclosure relates to compositions comprising an expressible nucleic acid sequence comprising, in a 5′ to 3′ orientation, a first nucleic acid sequence comprising a leader sequence, functional fragment thereof or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence encoding a retroviral polypeptide that is a component of a retroviral trimer, a functional fragment thereof or a pharmaceutically acceptable salt thereof. In some embodiments, the retroviral polypeptide that is a component of a retroviral trimer is a monomer of a retroviral trimer, such that, upon expression, the monomers spontaneously aggregate to form a trimeric retroviral polypeptide. In some embodiments, the expressible nucleic acid comprises a leader sequence. In some embodiments, the leader is an IgE or IgG leader sequence. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence and a second nucleic acid sequence, each of the first and second nucleic acid sequences encoding a retroviral ENV protein or variant thereof, the first and second nucleic acid sequences are non-contiguous and separated by at least one nucleic acid sequence encoding a linker. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence and a second nucleic acid sequence, each of the first and second nucleic acid sequences encoding a retroviral ENV protein or variant thereof, the first and second nucleic acid sequences are non-contiguous and separated by at least one nucleic acid sequence encoding a linker, wherein the retroviral ENV protein or variant thereof is free of a transmembrane domain. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence and a second nucleic acid sequence, each of the first and second nucleic acid sequences encoding a retroviral ENV protein or variant thereof, the first and second nucleic acid sequences are non-contiguous and separated by at least one nucleic acid sequence encoding a linker, wherein the retroviral ENV protein or variant thereof is free of a transmembrane domain and, upon expression is capable of self-assembly into a trimer. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence and a second nucleic acid sequence, each of the first and second nucleic acid sequences encoding a HIV-1 ENV protein or variant thereof, the first and second nucleic acid sequences are non-contiguous and separated by at least one nucleic acid sequence encoding a linker, wherein the HIV-1 ENV protein or variant thereof is free of the native transmembrane domain (gp41) and, upon expression is capable of self-assembly into a trimer. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence, a second nucleic acid sequence and a third nucleic acid sequence, each of the first, second and third nucleic acid sequences encoding a retroviral ENV monomer or variant thereof, the first, second and third nucleic acid sequences are non-contiguous and separated by at least one nucleic acid sequence encoding at least one linker.

Disclosed are compositions comprising an expressible nucleic acid sequence comprising a first nucleic acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to one or a plurality of: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8 and SEQ ID NO: 9 or a pharmaceutically acceptable salt thereof; and a second nucleotide sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to one or a plurality of: SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 59 SEQ ID NO: 60, SEQ ID NO: 62 SEQ ID NO: 63, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 90, SEQ ID NO: 91 or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the expressible nucleic acid sequence comprised in the disclosed composition comprises a first nucleic acid sequence encoding a polypeptide comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to one or a plurality of: SEQ ID NO: 7 and SEQ ID NO: 10 or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence encoding a polypeptide comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to one or a plurality of: SEQ ID NO: 55, SEQ ID NO: 58, SEQ ID NO: 61, SEQ ID NO: 64, SEQ ID NO:80, SEQ ID NO:83. SEQ ID NO:86, SEQ ID NO: 89, SEQ ID NO: 92 or a pharmaceutically acceptable salt of any of the foregoing.

Also disclosed are compositions comprising an expressible nucleic acid sequence comprising a nucleic acid sequence encoding a transmembrane domain free of an HIV ENV transmembrane domain (e.g., gp41). In some embodiments, the transmembrane domain comprises at least about 70% 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to SEQ ID NO: 230, SEQ ID NO: 231 or a pharmaceutically acceptable salt thereof; and a nucleotide sequence encoding a self-assembling polypeptide optionally fused to the transmembrane domain.

In some embodiments, the expressible nucleic acid sequence further comprises a nucleic acid sequence encoding at least one viral antigen or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence further comprises at least one nucleic acid sequence encoding a linker. Thus, also disclosed are compositions comprising an expressible nucleic acid sequence comprising a first nucleic acid sequence encoding a leader sequence or a pharmaceutically acceptable salt thereof; and a second nucleic acid sequence comprising sequence that encodes a self-assembling polypeptide or a pharmaceutically acceptable salt thereof; a third nucleic acid sequence encoding a linker sequence; and a fourth nucleic acid sequence comprising a sequence that encodes at least one viral antigen. In some embodiments, the expressible nucleic acid is operably linked to one or more regulatory sequences. In some embodiments, the expressible nucleic acid is part of a nucleic acid molecule, such as a vector or plasmid.

The disclosure also relates to any of the nucleic acid sequences disclosed herein as RNA, modified RNA or DNA-RNA hybrid molecules or pharmaceutically acceptable salts thereof. If the nucleic acid sequence of the disclosure is prepared as a mRNA sequence, the mRNA sequence may be modified with a polyA tail and/or a 5′ cap at the 5′ end and/or may be modified or encapsulated by lipid or lipid-like of the nucleic acid sequence. The nucleic acid sequences of the disclosure may have any one or a combination of modifications disclosed herein.

In some embodiments, the term “modification” relates to providing an RNA with a 5′-cap or 5′-cap analog. The term “5′-cap” refers to a cap structure found on the 5′-end of an mRNA molecule and generally consists of a guanosine nucleotide connected to the mRNA via an unusual 5′ to 5′ triphosphate linkage. In some embodiments, this guanosine is methylated at the 7-position. The term “conventional 5′-cap” refers to a naturally occurring RNA 5′-cap, preferably to the 7-methylguanosine cap (m 7G). In the context of the present disclosure, the term “5′-cap” includes a 5′-cap analog that resembles the RNA cap structure and is modified to possess the ability to stabilize RNA and/or enhance translation of RNA if attached thereto, preferably in vivo and/or in a cell.

The 5′ end of the RNA includes a cap structure having the following general formula:

wherein R₁ and R₂ are independently hydroxy or methoxy and W-, X- and Y-are independently oxygen, sulfur, selenium, or BH₃. In some embodiments, R₁ and R₂ are hydroxy and W-, X- and Y- are oxygen. In some embodiments, one of R₁ and R₂, preferably R₁ is hydroxy and the other is methoxy and W-, X- and Y- are oxygen. In some embodiments, R₁ and R₂ are hydroxy and one of W-, X- and Y-, preferably X- is sulfur, selenium, or BH₃, preferably sulfur, while the other are oxygen; and the nucleotide on the right hand side is bonded to the expressible RNA sequence through its 3′ group. In some embodiments, one of R₁ and R₂, preferably R₂ is hydroxy and the other is methoxy and one of W-, X- and Y-, preferably X- is sulfur, selenium, or BH 3, preferably sulfur while the other are oxygen. In some embodiments, the disclosure relates to compositions comprising a nucleotide sequence comprising an expressible RNA sequence encoding any of the one or more proteins disclosed herein.

In some embodiments, the term “modification” relates to modifications made to the expressible nucleic acids in order to tailor the vaccine induced responses. In some embodiments, such modifications comprise creating glycan sites so that glycosylation events can be obtained. In some embodiments, such glycan modifications or mutations decrease the bottom reactivity. In some embodiments, such glycan modifications or mutations increase antigen activity. In some embodiments, the methods of the disclosure are free of activating any mannose-binding lectin or complement process due to such glycan modifications or mutations.

1. Leader Sequence

Disclosed are nucleic acid sequences comprising a leader sequence or a pharmaceutically acceptable salt thereof “Signal peptide” and “leader sequence” are used interchangeably herein and refer to an amino acid sequence that can be linked at the amino terminus of a protein set forth herein. Signal peptides/leader sequences typically direct localization of a protein. Signal peptides/leader sequences used herein preferably facilitate secretion of the protein from the cell in which it is produced. Signal peptides/leader sequences are often cleaved from the remainder of the protein, often referred to as the mature protein, upon secretion from the cell. Signal peptides/leader sequences are linked at the N terminus of the protein.

In some embodiments, the leader sequence can be the nucleic acid sequence of ATGGACTGGACCTGGATTCTGTTCCTGGTGGCCGCCGCCACAAGGGTGCACAGC (SEQ ID NO: 1). In some embodiments, the leader sequence can have at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 1.

In some embodiments, the leader sequence can be the nucleic acid sequence ATGGACTGGACCTGGAGAATCCTGTTCCTGGTGGCCGCCGCCACCGGCACACAC GCCGATACACACTTCCCCATCTGCATCTTTTGCTGTGGCTGTTGCCATAGGTCCAA GTGTGGGATGTGCTGCAAAACT (SEQ ID NO:). In some embodiments, the leader sequence can have at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to any one or plurality of: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, and SEQ ID NO: 9. In some embodiments, the leader sequence is encoded as MDWTWRILFLVAAATGTHA (SEQ ID NO: 10) or a functional fragment that has at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 10. In some embodiments, the expressible nucleic acid sequence comprises a nucleic acid sequence encoding a leader that has at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to MDWTWILFLVAAATRVHS (SEQ ID NO: 7).

2. Self-Assembling Polypeptide as Particle Monomer

The disclosure relates to an expressible nucleic acid sequence comprising at least one domain that encodes a self-assembling polypeptide. In some embodiments, the self-assembling polypeptide is encoded by an antigen presenting cell that is transfected or transduced with a nucleic acid molecule comprising the expressible nucleic acid sequence that encodes the self-assembling polypeptide. In some embodiments, self-assembling polypeptides are monomeric forms of retroviral trimers or variants thereof. In some embodiments, the polypeptides are monomers of nanoparticle structural proteins that self-assemble into nanoparticles upon expression. In some embodiments, the nucleotide sequence encoding a self-assembling polypeptide and comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 151, SEQ ID NO: 152, or a pharmaceutically acceptable salt thereof. SEQ ID NO: 238 is the DNA sequence encoding lumizine synthase sequence of:

ATGCAGATCTACGAAGGAAAACTGACCGCTGAGGG ACTGAGGTTCGGAATTGTCGCAAGCCGCGCGAATC ACGCACTGGTGGATAGGCTGGTGGAAGGCGCTATC GACGCAATTGTCCGGCACGGCGGGAGAGAGGAAGA CATCACACTGGTGAGAGTCTGCGGCAGCTGGGAGA TTCCCGTGGCAGCTGGAGAACTGGCTCGAAAGGAG GACATCGATGCCGTGATCGCTATTGGGGTCCTGTG CCGAGGAGCAACTCCCAGCTTCGACTACATCGCCT CAGAAGTGAGCAAGGGGCTGGCTGATCTGTCCCTG GAGCTGAGGAAACCTATCACTTTTGGCGTGATTAC TGCCGACACCCTGGAACAGGCAATCGAGGCGGCCG GCACCTGCCATGGAAACAAAGGCTGGGAAGCAGCC CTGTGCGCTATTGAGATGGCAAATCTGTTCAAATC TCTGCGAGGAGGCTCCGGAGGATCTGGAGGGAGTG GAGGCTCAGGAGGAGGC.

In some embodiments, the lumizine synthase sequence is derived from hyperthermophilic bacterium Aquifex aeolicus. In some embodiments, other lumizine synthase sequences can be used. In some embodiments, the nucleotide sequence encoding a functional fragment of a self-assembling polypeptide comprising about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO:238. The disclosure also relates to the expressible nucleic acid sequence comprising one or a plurality of self-assembling polypeptides encoded by a first nucleic acid sequence comprising at least 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to the following:

(3BVE): GGGCTGAGTAAGGACATTATCAAGCTGCTGAACGA ACAGGTGAACAAAGAGATGCAGTCTAGCAACCTGT ACATGTCCATGAGCTCCTGGTGCTATACCCACTCT CTGGACGGAGCAGGCCTGTTCCTGTTTGATCACGC CGCCGAGGAGTACGAGCACGCCAAGAAGCTGATCA TCTTCCTGAATGAGAACAATGTGCCCGTGCAGCTG ACCTCTATCAGCGCCCCTGAGCACAAGTTCGAGGG CCTGACACAGATCTTTCAGAAGGCCTACGAGCACG AGCAGCACATCTCCGAGTCTATCAACAATATCGTG GACCACGCCATCAAGTCCAAGGATCACGCCACATT CAACTTTCTGCAGTGGTACGTGGCCGAGCAGCACG AGGAGGAGGTGCTGTTTAAGGACATCCTGGATAAG ATCGAGCTGATCGGCAATGAGAACCACGGGCTGTA CCTGGCAGATCAGTATGTCAAGGGCATCGCTAAGT CAAGGAAAAGC.

The disclosure also relates to the expressible nucleic acid sequence comprising one or a plurality of self-assembling polypeptides encoded by a first nucleic acid sequence comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to the following:

(RBE): CTGAGCATTGCCCCCACACTGATTAACCGGGACAA ACCCTACACCAAAGAGGAACTGATGGAGATTCTGA GACTGGCTATTATCGCTGAGCTGGACGCCATCAAC CTGTACGAGCAGATGGCCCGGTATTCTGAGGACGA GAATGTGCGCAAGATCCTGCTGGATGTGGCCAGGG AGGAGAAGGCACACGTGGGAGAGTTCATGGCCCTG CTGCTGAACCTGGACCCCGAGCAGGTGACCGAGCT GAAGGGCGGCTTTGAGGAGGTGAAGGAGCTGACAG GCATCGAGGCCCACATCAACGACAATAAGAAGGAG GAGAGCAACGTGGAGTATTTCGAGAAGCTGAGATC CGCCCTGCTGGATGGCGTGAATAAGGGCAGGAGCC TGCTGAAGCACCTGCCTGTGACCAGGATCGAGGGC CAGAGCTTCAGAGTGGACATCATCAAGTTTGAGGA TGGCGTGCGCGTGGTGAAGCAGGAGTACAAGCCCA TCCCTCTGCTGAAGAAGAAGTTCTACGTGGGCATC AGGGAGCTGAACGACGGCACCTACGATGTGAGCAT CGCCACAAAGGCCGGCGAGCTGCTGGTGAAGGACG AGGAGTCCCTGGTCATCCGCGAGATCCTGTCTACA GAGGGCATCAAGAAGATGAAGCTGAGCTCCTGGGA CAATCCAGAGGAGGCCCTGAACGATCTGATGAATG CCCTGCAGGAGGCATCTAACGCAAGCGCCGGACCA TTCGGCCTGATCATCAATCCCAAGAGATACGCCAA GCTGCTGAAGATCTATGAGAAGTCCGGCAAGATGC TGGTGGAGGTGCTGAAGGAGATCTTCCGGGGCGGC ATCATCGTGACCCTGAACATCGATGAGAACAAAGT GATCATCTTTGCCAACACCCCTGCCGTGCTGGACG TGGTGGTGGGACAGGATGTGACACTGCAGGAGCTG GGACCAGAGGGCGACGATGTGGCCTTTCTGGTGTC CGAGGCCATCGGCATCAGGATCAAGAATCCAGAGG CAATCGTGGTGCTGGAG.

The disclosure also relates to the expressible nucleic acid sequence comprising one or a plurality of self-assembling polypeptides encoded by a first nucleic acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity to the following SEQ ID NO:

(I3):

GAGAAAGCAGCCAAAGCAGAGGAAGCAGCACGGAA GATGGAAGAACTGTTCAAGAAGCACAAGATCGTGG CCGTGCTGAGGGCCAACTCCGTGGAGGAGGCCAAG AAGAAGGCCCTGGCCGTGTTCCTGGGCGGCGTGCA CCTGATCGAGATCACCTTTACAGTGCCCGACGCCG ATACCGTGATCAAGGAGCTGTCTTTCCTGAAGGAG ATGGGAGCAATCATCGGAGCAGGAACCGTGACAAG CGTGGAGCAGTGCAGAAAGGCCGTGGAGAGCGGCG CCGAGTTTATCGTGTCCCCTCACCTGGACGAGGAG ATCTCTCAGTTCTGTAAGGAGAAGGGCGTGTTTTA CATGCCAGGCGTGATGACCCCCACAGAGCTGGTGA AGGCCATGAAGCTGGGCCACACAATCCTGAAGCTG TTCCCTGGCGAGGTGGTGGGCCCACAGTTTGTGAA GGCCATGAAGGGCCCCTTCCCTAATGTGAAGTTTG TGCCCACCGGCGGCGTGAACCTGGATAACGTGTGC GAGTGGTTCAAGGCAGGCGTGCTGGCAGTGGGCGT GGGCAGCGCCCTGGTGAAGGGCACACCCGTGGAAG TCGCTGAGAAGGCAAAGGCATTCGTGGAAAAGATT AGGGGGTGTACTGAG.

In some embodiments, the expressible nucleic acid sequence comprises of any one or plurality of nucleic acid sequences encoding a self-assembling polypeptide and one or a plurality of nucleic acid sequences encoding a retroviral monomer or trimer. In some embodiments, the compositions or pharmaceutical compositions of the disclosure relate to nucleic acid sequences comprising at least a first expressible nucleic acid sequence comprising a domain with at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity to one or a plurality of: SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 178, and SEQ ID NO: 179.

3. Linker

The disclosure relates, in some embodiments, to an expressible nucleic acid sequence comprising a linker that fuses a first domain in a nucleic acid sequence to a second domain in the expressible nucleic acid sequence. In some embodiments, the expressible nucleic acid sequence comprises at least one nucleic acid sequence encoding a linker comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 10 or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence has one, two, three, four, five or more linkers in between each antigen domain and each independently selectable from one or a combination of an amino acid sequences at least about 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to: SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50 and SEQ ID NO: 52, or a pharmaceutically acceptable salt thereof. In some embodiments, the expressible nucleic acid sequence comprises GACACCATCACACTGCCATGCCGCCCT. In some embodiments, the at least one expressible nucleic acid sequence, encoding a linker, comprises a domain having at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to one or a combination of: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO: 31, SEQ ID NO:33 and SEQ ID NO:34 or a pharmaceutically acceptable salt thereof.

The disclosure also relates to the expressible nucleic acid sequence comprising one or a plurality of linker polypeptides encoded by a first nucleic acid sequence comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to the following: GGCGGCTCTGGCGGAAGTGGCGGAAGTGGGGGAAGTGGAGGCGGCGGAAGCGG GGGAGGCAGCGGGGGAGGG. The disclosure also relates to the expressible nucleic acid sequence comprising one or a plurality of linker polypeptides encoded by a first nucleic acid sequence comprising at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% sequence identity to the following: GGCGGAAGCG GCGGAAGCGGCGGGTCT.

In some aspects, the linker polypeptide is GSHSGSGGSGSGGHA or SHSGSGGSGSGGHA, or a polypeptide having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% sequence identity to SEQ ID NO: 47 or SEQ ID NO: 240.

A linker can be either flexible or rigid or a combination thereof. An example of a flexible linker is a GGS repeat. In some embodiments, the GGS can be repeated about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times, such that the composition comprising a nucleic acid comprises an expressible nucleic acid sequence encoding GGS from an amino terminus to a carboxy terminus in contiguous sequence 1, 2, 3, 4, 5, 6 or more times. An example of a rigid linker is 4QTL-115 Angstroms, single chain 3-helix bundle represented by the sequence:

NEDDMKKLYKQMVQELEKARDRMEKLYKEMVELIQ KAIELMRKIFQEVKQEVEKAIEEMKKLYDEAKKKI EQMIQQIKQGGDKQKMEELLKRAKEEMKKVKDKME KLLEKLKQIMQEAKQKMEKLLKQLKEEMKKMKEKM EKLLKEMKQRMEEVKKKMDGDDELLEKIKKNIDDL KKIAEDLIKKAEENIKEAKKIAEQLVKRAKQLIEK AKQVAEELIKKILQLIEKAKEIAEKVLKGLE.

In some embodiments, the composition comprises a nuclei acid sequence comprising a first expressible nucleic acid sequence comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more linkers, each linker is independently selectable from about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 to about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is independently selectable from a linker that is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, each linker is about 21 natural or non-natural nucleic acids in length.

In some embodiments, the nucleic acid sequence comprises or consists of Formula I for the expressible nucleic acid (NA) sequence in a 5′ to 3′ orientation:

[NA sequence for Leader Sequence-NA sequence for Viral Antigen Sequence or Self-Assembling Peptide-NA Sequence Linker-NA sequence for Viral Antigen Sequence or Self-Assembling Peptide]. In some embodiments, the multiple cloning site of a plasmid comprises, consists of or consists essentially of Formula I.

In some embodiments, the expressible nucleic acid sequence is within a multiple cloning site of a DNA molecule, such as a plasmid. In some embodiments, the length of each linker according to Formula I is different. For example, in some embodiments, the length of a first linker is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length, and the length of a second linker is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length, where the length of the first linker is different from the length of the second linker. Various configurations can be envisioned by the present disclosure, where Formula I comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more linkers wherein the linkers are of same, similar or different lengths.

In certain embodiments, two linkers can be used together, in a nucleotide sequence that encodes a fusion peptide. Accordingly, in some embodiments, the first linker is independently selectable from about 0 to about 25 natural or non-natural nucleic acids in length, about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 to about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, the second linker is independently selectable from about 0 to about 25, about 1 to about 25, about 2 to about 25, about 3 to about 25, about 4 to about 25, about 5 to about 25, about 6 to about 25, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to about 25, about 12 to about 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 16 to about 25, about 17 to about 25, about 18 to about 25, about 19 to about 25, about 20 to about 25, about 21 to about 25, about 22 to about 25, about 23 to about 25, about 24 to about 25 natural or non-natural nucleic acids in length. In some embodiments, the first linker is independently selectable from a linker that is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length. In some embodiments, the second linker is independently selectable from a linker that is about 0, about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25 natural or non-natural nucleic acids in length.

4. Self-Assembling Polypeptides as Viral Antigens

The disclosure relates to one or a plurality of nucleic acid molecules that comprise at least one expressible nucleic acid sequence, the expressible nucleic acid sequence comprises at least a first nucleic acid sequence encoding a first, a second and/or a third amino acid sequence, each first, second or third amino acid sequence comprising a viral antigen. In some embodiments, the at least first expressible nucleic acid sequence encodes a fusion protein, each fusion protein comprising at least a first, second, and third amino acid sequence contiguously linked by a linker sequence. The disclosure also relates to one or a plurality of nucleic acid molecules that comprise at least one expressible nucleic acid sequence, the expressible nucleic acid sequence comprises at least a first nucleic acid sequence encoding at least one self-assembling polypeptide. In some embodiments, the self-assembling peptide can be at least one self-assembling component of a nanoparticle or at least one retroviral monomer, the retorviral monomer capable of assembling into a retroviral trimer upon expression in a cell. In some embodiments, the at least one expressible nucleic acid sequence comprises nucleic acid sequence encoding a viral antigen free of a nucleic acid sequence encoding a self-assembling nanoparticle polypeptide. In some embodiments, the disclosure relates to a nucleic acid molecule comprising a nucleic acid sequence operably linked to a regulatory sequence and encoding a fusion peptide comprising one or a plurality of self-assembling peptides, wherein at least one of the self-assembling peptides is a self-assembling viral antigen. In some embodiments, upon administration to a subject, the composition comprising a nucleic acid comprising the expressible nucleic acid sequence is transfected or transduced into an antigen presenting cell which encodes the expressible nucleic acid sequence. After a plurality of expressible nucleic acid sequences are encoded, the self-assembling peptide assembles with other self-assembling peptides into a non-native form of a viral antigen. In some embodiments, non-native form of a viral antigen comprises a retroviral trimer exposing an amino acid sequence that is not naturally exposed or free of carbohydrate as compared to the native form or native form of its variant. Expression and presentation of the one or plurality of self-assembling peptides elicits an immune response against an epitope. In some embodiments, the epitope comprises a non-native secondary structure of the one or plurality of self-assembling peptides

In some embodiments, the viral antigen is an HIV-1 ENV protein or variant thereof. In some embodiments, the viral antigen is an HIV-1 ENV protein or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype A polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype B polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype C polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype D polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype E polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype F polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype G polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype H polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype J polypeptide or a variant thereof. In some embodiments, the viral antigen comprises an HIV-1, strain M, subtype K polypeptide or a variant thereof. In some embodiments, the viral antigen comprises a combination of one or a plurality of HIV-1, strain M polypeptides or variants thereof. In some embodiments, the nucleic acid molecule encodes a fusion peptide comprising one or a plurality of retroviral envelope polypeptides or functional fragments thereof. In some embodiments, the expressible nucleic acid sequence comprises a first nucleic acid sequence encoding, in a 5′ to 3′ orientation, at least three monomers of retroviral ENV proteins. In some embodiments, the at least three monomer polypeptides comprise a furin cleavage site. In some embodiments, the furin cleavage site comprises at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to RRRRRR. In some embodiments, the nucleic acid sequence encodes a polypeptide free of carbohydrate proximate to at least 30 amino acids from the carboxy end of the polypeptide. In some embodiments, the nucleic acid sequence encodes a polypeptide free of carbohydrate proximate to at least 20 amino acids from the carboxy end of the polypeptide. In some embodiments, the nucleic acid sequence encodes a polypeptide free of carbohydrate proximate to at least 10 amino acids from the carboxy end of the polypeptide. In some embodiments, the nucleic acid sequence encodes a polypeptide free of carbohydrate proximate to at least 50 amino acids from the carboxy end of the polypeptide.

In some embodiments, the expressible nucleic acid sequence comprises a nucleic acid sequence encoding one, two, three or more monomer or trimer peptides comprising any one or more of the following sequences or a sequence that comprises at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the following sequences in Table X:

TABLE X BG505_SOSIP_MD39 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILLTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQA RNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLANEHYLRDQQLLGIWG CSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQQIIYGLLEESQNQQE KNEQDLLALD BG505_MD39_GRSF AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQA RNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWG CSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLNWSKEISNYTQIIYGLLEESQNQQE KNNQSLLALD BG505_SOSIP_MD39_CPG9.2 GGNSSGSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQH LLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLS EIWDNMTWLNWSKEISNYTQIIYGLLEESQNQNESNEQDLGGNGSGGGSGSGGNGSS GLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLE NVTEEFNMWEKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDM RGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNT SAITQACPKVSFEPIPTIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVST QLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFY YTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIRFAQSSGGDLEVTTH SFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAM YAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIE PLGVAPTRCNRS BG505_SOSIP_MD39_link14 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLQDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALD BG505_SOSIP_MD39_trimer string 1 monomer 1 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALD BG505_SOSIP_MD39_trimer string 1 monomer 2 AENLLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALD BG505_SOSIP_MD39_trimer string 1 monomer 3 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDD MRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCN TSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVS TQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFY YTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTH SFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAM YAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIE PLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLFFLGAAGSTMGAASMTLT VQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLG IWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQN QQEKNEQDLLALD BG505_SOSIP_MD39_trimer string 1 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTVNTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVIGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEK HNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLLWDQSLKPCV KLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLLDVVQI NENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFN GTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILLVQLNTPVQI NCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKH FGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLLFNSTWISNTSVQGSNSTGSND SITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGG GDMRDNWRSELLYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVIGIGA VSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGI KQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTW LQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKD AETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVE QMHEDIISLWDQSLKPCVKLTPLCVTLQCTVNTNNITDDMRGELKNCSFNMTTELRD KKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHY CAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSEN ITNNAKNILLVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKA TWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLIL TRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHS GSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLL RAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWWGCSGKLICCTNVPWNS SWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD BG505_SOSIP_MD39_trimer string 2 (TS2) AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELLYKYK VVKIEPLLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGSGSGAENLWVTVYYGVPVWKDAETTLFCASDAKAY ETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSL KPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLD VVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDK KFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNT PVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQL RKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNST GSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETF RPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAV GIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDT HWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDN MTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGAENLWVTVYY GVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNM WKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSF NMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKV SFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAE EEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQ AHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYC NTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRC VSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCK RRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGI VQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLIC CTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDL LALD BG505_MD39 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALD BG505_MD39+linker AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGGSGGSGGSGGSGGSGGS BG505_MD39_link14_gp140-PDGFR AENLWVTVYYGVPVWEKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWOQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGGSGGSGGSGGSGGSGGSNAVGQDTQEVIVVPHSLPF KVVVISAILALVVLTIISLILLIMLWQKKPR BG505_MD39_gp140_foldon-PDGFR AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGP QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGGSGGSGGGYIPEAPRDGQAYVRKDGEWVLLSTFLGG SGGSGGSGGSNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKKPR BG505_MD39_TS1_gp140 AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKDAETTLFCASDAKAYETE KHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPC VKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQ INENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFN GTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQT NCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKH FGNNTIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSND SITLPCRIKQIINMWOQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGG GDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGA VSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGI KQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTW LQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWEKD AETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVE QMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRD KKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHY CAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSEN ITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKA TWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLIL TRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHS GSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLL RAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNS SWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD BG505_MD39_TS1_gp140-PDGFR AENLWVTVYYGVPVWEKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTN NITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYR LINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIK PVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPG QAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLE VTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRI GQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAA SMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLL EESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWDKAETTLFCASDAKAYETEK HNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCV KLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQI NENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFN GTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQI NCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKH FGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSND SITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGG GDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGA VSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGI KQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSSWSNRNLSEIWDNMTW LQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKD AETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVE QMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRD KKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHY CAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSEN ITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKA TWENTLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLIL TRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHS GSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLL RAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNS SWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGGS GGSGGSGGSGGSGGSNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIML WQKKPR TRO11_AY835445_MD39_L14G8 MDWTWILFLVAAATRVHSQGQLWVTVYYGVPVWKDASTTLFCASDAYAK DTEVHNVWATHACVPTDPNPQEVVLGNVTENFNMWKNNMVDQMHEDIISLWDQS LKPCVKLTPLCVTLNCTDNITNTNTNSSKNSSTHSYNNSLEGEMKNCSFNITAGIRDK VKKEYALFYKLDVVPIEEDKDTNKTTYRLRSCNTSVITQACPKVTFEPIPIHYCAPAG FAILCNDKKFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSENFTNNA KTIIVQLNESIANINCTRPNNNTVRSIHIGPGRAFYYTGDIIGDIRQAHCNISRTEWNSTL RQIVTKLREQLGDPNKTIIFAQSSGGDTEITMHSFNCGGEFFYCNTTKLFNSTWNGNN TTESDSTGENITLPCRIKQIINLWQEVGKAMYAPPIKGQISCSSNITGLLLTRDGGNNN SSGPETFRPGGGNMKDNWRSELYKYKVIKIEPLGVAPTRCKRRVVGSHSGSGGSGSGS GHAAVGTLGAMSLGFGAAGSTMGAASVTLTVQARLLLSGIVQQQNNLLRAPEQQ HMLQDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNASWSNKS LNNIWENMTWMNWSREIDNYTDLIYILLEKSQIQQEKNNQSLLELD Sequence in bold is th IgE leader sequence; underlined  sequence is the linker sequence; double underlined amino acids are glycan mutations. TRO11_MD39_L14G8_gp120 QGQLWVTVYYGVPVWKDASTTLFCASDAKAYDTE V HNVWATHACVPTDP NPQEVVLGNVTENFNMWKNNMVDQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDNI TNTNTNSSKNSSTHSYNNSLEGEMKNCSFNITAGIRDKVKKEYALFYKLDVVPIEED KDTNKTTYRLRSCNTSVITQACPKVTFEPIPIHYCATAGFAILKCNDKKFNGTGPCTN VSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSENFTNNAKTIIVQLNESIAINCTRPNN NTVRSIHIGPGRAFYYTGDIIGDIRQAHCNISRTEWNSTLRQIVTKLREQLGDPNKTIIF AQSSGGDTEITMHSFNCGGEFFYCNTTKLFNSTWNGNNTTESDSTGENITLPCRIKQII NLWQEVGKAMYAPPIKGQISCSSNITGLLLTRDGGNNNSSGPETFRPGGGNMKDNW RSELYKYKVIKIEPLGVAPTRCKRRVV TRO11_MD39_L14G8_gp41 AVGTLGAMSLGFLGAAGSTMGAASVTLTVQARLLLSGIVQQQNNLLRAPEP QQHMLQDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNASWSN KSLNNIWENMTWMNWSREIDNYTDLIYILLEKSQIQQEKNNQSLLELD Bolded residues are glycans X2278_FJ817366_MD39_L14G8 MDWTWILFLVAAATRVHSTNNLWVTVYYGVPVWKEATTTLFCASEAKAY DTEVHNIWATHACVPTDPNPQEMELKNVTENFNMWKNNMVEQMHEDIISLWDQSL KPCVKLTPLCVTLDCTNINSTNSTNNTSSNSKMEETIGVIKNCSFNVTTNIRDKVKKE NALFYSLDLVSIGNSNTSYRLISCNTSIITQACPKVSFDPIPIHYCAPAGFAILKCRDKKF NGTGPCRNVSSVQCTHGIRPVVSTQLLLNGSLAEEEIIIRSANLTDNAKTIIIQLNETIQI NCTRPNNNTVRSIPIGPGRTFYYTGDIIGDIRKAYCNISATKWNNTLRQIAEKLREKFN KTIIFAQSSGGDPEVVRHTFNCGGEFFYCNSSQLFNSTWYSNGTSNGGLNNSANITLP CRIKQIINLWQEVGKAMYAPPIKGVINCLSNITGIILTRDGGENNGTTETFRPGGGDM RDNWRSELYKYKVVIEPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLG FLGLAGSTMGAASVTLTVQARLLLSGIVQQQNNLLRAPEPQQQLLQDTHWGIKQLQ ARVLALEHYLKDQQLLGIWGCSGKLICCTTVPWNASWSNKSYNQIWNNMTWMNW SREIDNYTNLIYNLIEESQSQQEKNNLSLLQLD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined amino acids comprise glycan mutations. X22798_MD39_L14G8_gp120 TNNLWVTVYYGVPVWKEATTTLFCASEAKAYDTEVHNIWATHACVPTDPNP QEMELKNVTENFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLDCTNINST NSTNNTSSNSKMEETIGVIKNCSFNVTTNIRDKVKKENALFYSLDLVSIGNSNTSYRLI SCNTSIITQACPKVSFDPIPIHYCAPAGFAILKCRDKKFNGTGPCRNVSSVQCTHGIRPV VSTQLLLNGSLAEEEIIIRSANLTDNAKTIIIQLNETIQINCTRPNNNTVRSIPIGPGRTFY YTGDIIGDIRKAYCNISATKWNNTLRQIAEKLREKFNKTIIFAQSSGGDPEVVRHTFNC GGEFFYCNSSQLFNSTWYSNGTSNGGLNNSANITLPCRIKQIINLWQEVGKAMYAPPI KGVINCLSNITGIILTRDGGENNGTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGIA PTKCKRRVV X22798_MD39_L14G8_gp41 AVGLGAVSLGFLGLAGSTMGAAVTLTVQARLLLSGIVQQQNNLLRAPEPQQ QLLQDTHWGIKQLQARVLALEHYLKDQQLLGIWGCSGKLICCTTVPWNASWSNKS YNQIWNNMTWMNWSREIDNYTNLIYNLIEESQSQQEKNNLSLLQLD double underlined amino acid are glycan mutations 398F1_HM215312_MD39_L14G8 MDWTWILFLVAAATRVHSMGNLWVTVYYGVPVWKDAETTLFCASDAKA YHTEVHNVWATHACVPTDPNPQEINLENVTEEFNMWKNKMVEQMHEDIISLWDQS LKPCVQLTPLCVTLDCQYNVTNINSTSDMAREINNCSYNITTELRDREQKVYSLFYRS DIVQMNSDNSSKYRLINCNTSAIKQACPKVTFEPIPIHYCAPAGFAILKCKDKEFNGTG PCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEKVIIRSENITDNAKNIIVQLKEPVKINC TRPNNNTVKSVRIGPGQTFYYTGEIIGDIRQAHCNVSKAHWENTLQEVANQLKLMIH SNKTIIFANSSGGDLEITTHSFNCGGEFFYCYTSGLFNYTFNDTSTNSTESKSNDTITLQ CRIKQIINMWQRAGQAVYAPPIPGIIRCESNITGLILTRDGGNNNSNTNETFRPGGGDM RDNWRSELYRYKVVKIEPIGVAPTTCKRRVVGSHSGSGGSGSGGHAVVGIGAVSLGF LGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLKA RVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSLGEIWDNMTWLNWSK EIENYTQIIYELIEESQNQQEKNNQSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined amino acids are glycan mutations. MGNLWVTVYYGVPVWKDAETTLFCASDAKAYHTEVHNVWATHACVPTDP NPQEINLENVTEEFNMWKNKMVEQMHEDIISLWDQSLKPCVQLTPLCVTLDCQYNV TNINSTSDMAREINNCSYNITTELRDREQKVYSLFYRSDIVQMNSDNSSKYRLINCNT SAIKQACPKVTFEPIPIHYCAPAGFAILKCKDKEFNGTGPCKNVSTVQCTHGIKPVVST QLLLNGSLAEEKVIIRSENITDNAKNIIVQLKEPVKINCTRPNNNTVKSVRIGPGQTFY YTGEIIGDIRQAHCNVSKAHWENTLQEVANQLKLMIHSNKTIIFANSSGGDLEITTHSF NCGGEFFYCYTSGLFNYTFNDTSTNSTESKSNDTITLQCRIKQIINMWQRAGQAVYAP PIPGIIRCESNITGLILTRDGGNNNSNTNETFRPGGGDMRDNWRSELYRYKVVKIEPIG VAPTTCKRRVV AVGIGAVSLFLGAAGSTGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQH LLKDTHWGIKQLKARVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSLG EIWDNMTWLNWSKEIENYTQIIYELIEESQNQQEKNNQSLLALD double underlined amino acids are glycan mutations 246F3_HM215279_MD39_L14G8 MDWTWILFLVAAATRVHSMQDLWVTVYYGVPVWKDAKTTLFCASDAKA YEKEVHNVWATHACVPTDPNPQEIVMANVTEEFNMWKNNMVEQMHEDIISLWDQS LKPCVKLTPLCVTLDCKDYNYSITNNSTGMEGEIKNCSYNITTELRDKRQKVYSLFY RLDVVQINDSNDRNNSQYRLINCNTTTMTQACPKVTFDPIPIHYCAPAGFAILKCNNK TFNGKGPCNNVSSVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTDNVKTIIVHLNE SVEINCTRPNNNTVKSVRIGPGQTFYYTGDIIGNIRQAHCTVNKTEWNTALTRVSKKL KEYFPNKTIAFQPSSGGDLEITTFSFNCRGEFFYCNTSDLFNGTFNETSGQFNSTFNSTL QCRIKQIINMWQEVGQAMYAPPIAGSITCISNITGLILTRDGGNTNSTKETFRPGGGN MRDNWRSELYKYKVVKIEPLGVAPTKCRRRVVGSHSGSGGSGSGGHAAVGIGAVSI GFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQ ARVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSQDEIWDNMTWLNWS KEISNYTQIIYNLIEESQTQQELNNRSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined  amino acids are glycan mutations MQDLWVTVYYGVPVWKDAKTTLFCASDAKAYEKEVHNVWATHACVPTDP NPQEIVMANVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLDCKDY NYSITNNSTGMEGEIKNCSYNITTELRDKRQKVYSLFYRLDVVQINDSNDRNNSQYR LINCNTTTMTQACPKVTFDPIPIHYCAPAGFAILKCNNKTFNGKGPCNNVSSVQCTHG IKPVVSTQLLLNGSLAEKEIIIRSENLTDNVKTIIVHLNESVEINCTRPNNNTVKSVRIGP GQTFYYTGDIIGNIRQAHCTVNKTEWNTALTRVSKKLKEYFPNKTIAFQPSSGGDLEI TTFSFNCRGEFFYCNTSDLEFNGTFNETSGQFNSTFNSTLQCRIKQIINMWQEVGQAMY APPIAGSITCISNITGLILTRDGGNTNSTKETFRPGGGNMRDNWRSELYKYKVVKIEPL GVAPTKCRRRVV AVGIGAVSIGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQH LLKDTHWGIKQLQARVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSQ DEIWDNMTWLNWSKEISNYTQIIYNLIEESQTQQELNNRSLLALD double underlined amino acids are glcan mutations CE0217_FJ443575_MD39_L14G8 MDWTWILFLVAAATRVHSAKDMWVTVYYGVPVWREAKTTLFCASDAKA YEREVHNVWATHACVPTDPNPQERVLENVTENFNMWKNNMVDQMHEDIISLWDEA LKPCIKLTPLCVTLNCGNAIVNESTIEGMKNCSFNVTTELKDKKKKEYALFYKLDVV PLNGENNNSNKNFSEYRLINCNTSTITQACPKVSFDPIPIHYCAPAGFAILKCNNETF NGTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTNNAKIIIVHLNNPV KIICTRPGNNTVKSMRIGPGQTFYYTGDIIGDIRRAYCNISEKTWYDTLKNVSDKFQE HFPNASIEFKPSAGGDLEITTHSFNCRGEFFYCDTSELFNGTYNNSTYNSSNNITLQCKI KQIINMWQGVGRAMYAPPIAGNITCESNITGLLLTRDGGNNKSTPETFRPGGGDMRD NWRSELYKYKVVEIKPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGMGAVSLGFL GAAGSTMGAASLTLTVQARQLLSGIVQQQNNLLRAPEPQQHMLQDTHWGIKQLQA RVLAIEHYLTDQQLLGIWGCSGKLICCTNVPWNNSWSSNKSSYEDIWGRNMTWMNWS REINNYTNTIYRLLIKSSQNQQEKNNKSLLELD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined  amino acids are glycan mutations AKDMWVTVYYGVPVWREAKTTLFCASDAKAYEREVHNVWATHACVPTDP NPQERVLENVTENFNMWKNNMVDQMHEDIISSLWDESLKPCIKLTPLCVTLNCGNAI VNESTIEGMKNCSFNVTTELKDKKKKEYALFYKLDVVPLNGENNNSNSKNFSEYRLI NCNTSTITQACPKVSFDPIPIHYCAPAGFAILKCNNETFNGTGPCNNVSTVQCTHGIKP VVSTQLLLNGSLAEKEIIIRSENLTNNAKIIIVHLNNPVKIICTRPGNNTVKSMRIGPGQ TFYYTGDIIGDIRRAYCNISEKTWYDTLKNVSDKFQEHFPNASIEFKPSAGGDLEITTH SFNCRGEFFYCDTSELFNGTYNNSTYNSSNNITLQCKIKQIINMWQGVGRAMYAPPIA GNITCESNITGLLLTRDGGNNKSTPETFRPGGGDMRDNWRSELYKYKVVEIKPLGIAP TKCKRRVV AVGMGAVSLGFLGAAGSTMGASLTLTVQARQLLSGIVQQQNNLLRAPEPQ QHMLQDTHWGIKQLQARVLAIEHYLTDQQLLGIWGCSGKLICCTNVPWNNSWSNK SYEDIWGRNMTWMNWSREINNYTNTIYRLLIKSQNQQEKNNKSLLELD double underlined amino acids are glycan mutations C31176_FJ444437_MD39_L14G8 MDWTWILFLVAAATRVHIVGNLWVTVYYGVPVWKEAKTTLFCASDAKAY EKEVHNVWATHACVPTDPNPQEMVLENVTENFNMWKNDMVDQMHEDVISLWDQ SLKPCVKLTPLCVTLTCTNTTVSNGSSNSNANFEEMKNCSFNATTEIKDKKKNEYAL FYKLDIVPLNNSSGKYRLINCNTSAIAQACPKVTFEPIPIHYCAPAGYAILKCNNKTFN GTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTNNAKTIIIHLNESVGI VCTRPSNNTVKSIRIGPGQTFYYTGDIIGDIRQAHCNVSKQNWNRTLQQVGRKLAEH FPNRNITFAHSSGGDLEITTHSFNCRGEFFYCNTSGLGNGTYHPNGTYNETAVNSSDTI TLQCRIKQIINMWQEVGRAMYAPPIAGNITCNSTITGLLLTRDGGINQTGEEIFRPGGG DMRDNWRNELYKYKVVEIKPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGIGAVS LGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHMLQDTHQGIKQ LQARVLAIEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNRSQEDIWNNMTWMN WSREIDNYTHTIYSLLEESQIQQEKNNKSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined amino acids are glycan mutations VGNLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVHNVWATHACVPTDP NPQEMVLENVTENFNMWKNDMVDQMHEDVISLWDQSLKPCVKLTPLCVTLTCTNT TVSNGSSNSNANFEEMKNCSFNATTEIKDKKKNEYALFYKLDIVPLNNSSGKYRLIN CNTSIAQACPKVTFEPIPIHYCAPAGYAILKCNNKTFNGTGPCNNVSTVQCTHGIKP VVSTQLLLNGSLAEKEIIIRSENLTNNAKTIIIHLNESVGIVCTRPSNNTVKSIRIGPGQT FYYTGDIIGDIRQAHCNVSKQNWNRTLQQVGRKLAEHFPNRNITFAHSSGGDLEITTH SFNCRGEFFYCNTSGLFNGTYHPNGTYNETAVNSSDTITLQCRIKQIINMWQEVGRA MYAPPIAGNITCNSTITGLLLTRDGGINQTGEEIFRPGGGDMRDNWRNELYKYKVVEI KPLGIAPTKCKRRVV AVGIGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEQQH MLQDTHWGIKQLQARVLAIEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNRSQE DIWNNMTWMNWSREIDNYTHTIYSLLEESQIQQEKNNKSLLALD double underlined amino acids are glycan mutations 25710_EF117271_MD39_L14G8 MDWTWILFLVAAATRVHSGGNLWVTVYYGVPVWKEATTTLFCASDAKAY DKEVHNVWATHACVPTDPNPQEMVLGNVTENFNMWKNEMVNQMHEDVISLWDQ SLKPCVKLTPLCVTLECSNVTYNESMKEVKNCSFNLTTELRDKKQKVHALFYRLDIV PLNDTEKKNSSRPYRLINCNTSAITQACPKVTFDPIPIHYCTPAGYAILKCNDKKFNGT GPCHKVSTVQCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLTNNAKTIIVHLNQSVEIVC ARPSNNTVTSIRIGPGQTFYYTGAITGDIRQAHCNISKDKWNETLQRVGEKLAEHFPN KTIKFASSSGGDLEITTHSFNCRGEFFYCNTSGLFNGTFNGTYVSPNSTDSNSSSIITIPC RIKQIINMWQEVGRAMYAPPIAGNITCKSNITGLLLVRDGGTGSESNKTEIFRPGGGD MRDNWRSELYKYKVVEIKPLGVAPTKCKRRVVGSHSGSGGSGSGGHAAVGIGAVSL GFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIKQLQ TRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNYSWSNRSQDDIWDNMTWMNWS KEISNYTNTIYKLLEDSQIQQEKNNKSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined  amino acids are glycan mutations GGNLWVTVYYGVPVWKEATTTLFCASDAKAYDKEVHNVWATHACVPTDP NPQEMVLGNVTENFNMWKNEMVNQMHEDISLWDQSLKPCVKLTPLCVTLECSNV TYNESMKEVKNCSFNLTTELRDKKQKVHALFYRLDIVPLNDTEKKNSSRPYRLINCN TSAITQACPKVTFDPIPIHYCTPAGYAILKCNDKKFNGTGPCHKVSTVQCTHGIKPVV STQLLLNGSLAEGEIIIRSENLTNNAKTIIVHLNQSVEIVCARPSNNTVTSIRIGPGQTFY YTGAITGDIRQAHCNISKCKWNETLQRVGEKLAEHFPNKTIKFASSSGGDLEITTHSF NCRGEFFYCNTSGLFNGTFNGTYVSPNSTDSNSSSIITIPCRIKQIINMWQEVGRAMYA PIIAGNITCKSNITGLLLVRDGGTGSESNKTEIFRPGGGDMRDNWRSELYKYKVVEIK PLGVAPTKCKRRVV AVGIGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQH LLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNYSWSNRSQD DIWDNMTWMNWSKEISNYTNTIYKLLEDSQIQQEKNNKSLLALD double underlined amino acids are glycan mutations BJOX2000_HM215364_MD39_L14G8 MDWTWILFLVAAATRVHIVGNLWVTVYYGVPVWKEATTTLFCASDAKAY DTEVHNVWATHACVPTDPDPQEMFLENVTENFNMWKNNMVDQMHEDVISLWDQS LKPCVKLTPLCVTLECKNVNSSSSDTKNGTDPEMKNCSFNATTELRDRKQKVYALF YKLDIVPLNEKNSSEYRLINCNTSTITQACPKVTFDPIPIHYCTPAGYAILKCNDEKFN GTGPCSNVSTVQCTHGIKPVVSTQLLLNGSLAEKGIIIRSENLTNNVKTIIVHLNQSVEI LCIRPNNNTVKSIRIGPGQTFYYTGEIIGDIRQAHCNISGKVWNETLQRVGEKLAEYFP NKTIKFASSSGGDLEITTHSFNCGGEFFYCNTSKLFNGTFNGTYMPNVTEGNSTISIPC RIKQIINMWQKVGRAMYAPPIEGNITCKSKITGLLLERDGGPENDTEIFRPGGGDMRN NWRSELYKYKVVEIKPLGVAPTECKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFL GVAGSTMGAASMALTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIKQLQTR VLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQEEIWENMTWMNWSKEI SNYTDTIYRLLEDSQNQQERNNKSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined amino acids are glycan mutations VGNLWVTVYYGVPVWKEATTLFCASDAKAYDTEVHNVWATHACVPTDPD PQEMFLENVTENFNMWKNNMVDQMHEDVISLWDQSLKPCVKLTPLCVTLECKNVN SSSSDTKNGTDPEMKNCSFNATTELRDRKQKVYALFYKLDIVPLNEKNSSEYRLINC NTSTITQACPKVTFDPIPIHYCTPAGYAILKCNDEKFNGTGPCSNVSTVQCTHGIKPVV STQLLLNGSLAEKGIIIRSENLTNNVKTIIVHLNQSVEILCIRPNNNTVKSIRIGPGQTFY YTGEIIGDIRQAHCNISGKVWNETLQRVGEKLAEYFPNKTIKFASSSGGDLEITTHSFN CGGEFFYCNTSKLFNGTFNGTYMPNVTEGNSTISIPCRIKQIINMWQKVGRAMYAPPI EGNITCKSKITGLLLERDGGPENDTEIFRPGGGDMRNNWRSELYKYKVVEIKPLGVA PTECKRRVV AVGIGAVSLGFLGVAGSTMGAASMALTVQARQLLSGIVQQQSNLLRAPEPQQ HLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQ EEIWENMTWMNWSKEISNYTDTIYRLLEDSQNQQERNNKSLLALD double underlined amino acids are glycan mutations CH119_EF117261_MD39_L14G8 MDWTWILFLVAAATRVHIVGNLWVTVYYGVPVWKEATTTLFCASDAKAY DTEVHNVWATHACVPTDPSPQELVLENVTENFNMWKNEMVNQMHEDVISLWDQS LKPCVKLTPLCVTLECSKVSNNETDKYNGTEEMKNCSFNATTVVRDRQQKVYALFY RLDIVPLTEKNSSENSSKYYRLINCNTSAITQACPKVSFEPIPIHYCTPAGYAILKCNDK TFNGTGPCHNVSTVQCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLTNNVKTILVHLNQ SVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGDIRQAHCNISKWHETLKRVSEKLAEH FPNKTINFTSSSGGDLEITTHSFTCRGEFFYCNTSGLFNSTYMPNGTYLHGDTNSNSSI TIPCRIKQIINMWQEVGRAMYAPPIEGNITCKSNITGLLLVRDGGTESNNTETNNTEIF RPGGGDMRDNWRSELYKYKVVEIKPLGVAPTACKRRVVGSHSGSGGSGSGGHAAV GIGAVSLGFLGVAGSTMGAASMTLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDT HWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQKEIWDN MTWMNWSKEISNYTNTIYKLLEDSQNQQESNNKSLLALD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined  amino acids are glycan mutations VGNLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPS PQELVLENVTENFNMWKNEMVNQMHEDVISLWDQSLKPCVKLTPLCVTLECSKVS NNETDKYNGTEEMKNCSFNATTVVRDRQQKVYALFYRLDIVPLTEKNSSENSSKYY RLINCNTSAITQACPKVSFEPIPIHYCTPAGYAILKCNDKTFNGTGPCHNVSTVQCTHG IKPVVSTQLLLNGSLAEGEIIIRSENLTNNVKTILVHLNQSVEIVCTRPNNNTVKSIRIGP GQTFYYTGDIIGDIRQAHCNISKWHETLKRVSEKLAEHFPNKTINFTSSSGGDLEITTH SFTCRGEFFYCNTSGLFNSTYMPNGTYLHGDTNSNSSITIPCRIKQIINMWQEVGRAM YAPPIEGNITCKSNITGLLLVRDGGTESNNTETNNTEIFRPGGGDMRDNWRSELYKYK VVEIKPLGVAPTACKRRVV AVGIGAVSLGFLGVAGSTMGAASMTLTVQARQLLSGIVQQQSNLLRAPEPQQ HLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQ KEIWDNMTWMNWSKEISNYTNTIYKLLEDSQNQQESNNKSLLALD double underlined amino acids are glycan mutations X1632_FJ817370_MD39_L14G8 SEQ ID NO: MDWTWILFLVAAATRVHSSNNLWVTVYYGVPVWEDADTTLFCASDAKAY STESHNVWATHACVPTDPNPQEIYLENVTEDFNMWENNMVEQMQEDIISLWDESLK PCVKLTPLCVTLTCTNVTNVTDSVGTNSRLKGYKEELKNCSFNTTTEIRDKKKQEYA LFYKLDIVPINDNSNNSNGYRLINCNVSTIKQACPKVSFDPIPIHYCAPAGFAILKCRD KEFNGTGTCRNVSTVQCTHGIKPVVSTQLLLNGSLAEGDIIIRSENITDNAKTIIVHLN KTVSITCTRPNNNTVKSIRIGPGQALYYTGAIIGDTRQAHCNINGSEWYEMIQNVKNK LNETFKKNITFAPSSGGDLEITTHSFNCRGEFFYCNTSELFNSSHLFNGSTLSTNGTITL PCRIKQIVRMWQRVGQAMYAPPIAGNITCRSNITGLLLTRDGGTNKDTNEAETFRPG GGDMRDNWRSELYKYKVVKIKPLGVAPTRCRRRVVGSHSGSGGSGSGGHAAIGLG TVSLGFLGTAGSTMGAASITLTVQVRQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGI KQLQARVLAVEHYLKDQQILGIWGCSGKLICCTNVPWNSSWSNKSYSDIWDNLTWI NWSREISNYTQQIYTLLEESQNQQEKNNQSLLALD Sequence in bold is the IgE leader sequence;  underlined sequence is the linker sequence; double underlined amino acids are glycan mutations SNNLWVTVYYGVPVWEDADTTLFCASDAKAYSTESHNVWATHACVPTDPN PQEIYLENVTEDFNMWENNMVEQMQEDIISLWDESLKPCVKLTPLCVTLTCTNVTN VTDSVGTNSRLKGYKEELKNCSFNTTTEIRDKKKQEYALFYKLDIVPINDNSNNSNG YRLINCNVSTIKQACPKVSFDPIPIHYCAPAGFAILKCRDKEFNGTGTCRNVSTVQCTH GIKPVVSTQLLLNGSLAEGDIIIRSENITDNAKTIIVHLNKTVSITCTRPNNNTVKSIRIG PGQALYYTGAIIGDTRQAHCNINGSEWYEMIQNVKNKLNETFKKNITFAPSSGGDLEI TTHSFNCRGEFFYCNTSELFNSSHLFNGSTLSTNGTITLPCRIKQIVRMWQRVGQAMY APPIAGNITCRSNITGLLLTRDGGTNKDTNEAETFRPGGGDMRDNWRSELYKYKVVK IKPLGVAPTRCRRRVV AIGLGTVSLGFLGTAGSTMGAASITLTVQVRQLLSGIVQQQSNLLRAPEPQQH LLQDTHWGIKQLQARVLAVEHYLKDQQILGIWGCSGKLICCTNVPWNSSWSNKYS DIWDNLTWINWSREISNYTQQIYTLLEESQNQQEKNNQSLLALD double underlined amino acids are glycan mutations CNE8_HM215427_MD39_L14G8 MDWTWILFLVAAATRVHSSDNLWVTVYYGVPVWRDADTTLFCASDAKAY DTEVHNVWATHACVPTDPNPQEIHLENVTENFNMWKNKMAEQMQEDVISLWDESL KPCVQLTPLCVTLNCTNANLNATVNASTTIGNITDEVRNCSFNTTTELRDKKQNVYA LFYKLDIVPINNNSEYRLINCNTSVIKQACPKVSFDPIPIHYCAPAGYAILRCNDKNFN GTGPCKNVSSVQCTHGIKPVVSTQLLLNGSLAEDEIIIRSENLTDNVKTIIVHLNKSVEI NCTRPSNNTVTSVRIGPGQVFYYTGDIIGDIRKAYCEINRTKWHETLKQVATKLREHF NKTIIFQPPSGGDIEITMHHFNCRGEFFYCNTTKLFNSTWGENTTMEGHNDTIVLPCRI KQIVNMWQGVGQAMYAPPIRGSINCVSNITGILLTRDGGTNMSNETFRPGGGNIKDN WRSELYKYKVVEIEPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGIGAMSFGFLGA AGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIKQLQARVL AVEHYLKDQKFLGLWGCSGKIICCTAVPWNSTWSNRSYEEIWDNMTWINWSREISN YTSQIYEILTESQNQQDRNNKSLLELD Sequence in bold is the IgE leader sequence;  underlined sequence is the linker sequence; double  underlined amino acids are glycan mutations SDNLWVTVYYGVPVWRDADTTLFCASDAKAYDTEVHNVWATHACVPTDPN PQEIHLENVTENFNMWKNKMAEQMQEDVISLWDESLKPCVQLTPLCVTLNCTNANL NATVNASTTIGNITDEVRNCSFNTTTELRDKKQNVYALFYKLDIVPINNNSEYRLINC NTSVIKQACPKVSFDPIPIHYCAPAGYAILRCNDKNFNGTGPCKNVSSVQCTHGIKPV VSTQLLLNGSLAEDEIIIRSENLTDNVKTIIVHLNKSVEINCTRPSNNTVTSVRIGPGQV FYYTGDIIGDIRKAYCEINRTKWHETLKQVATKLREHFNKTIIFQPPSGGDIEITMHHF NCRGEFFYCNTTKLFNSTWGENTTMEGHNDTIVLPCRIKQIVNMWQGVGQAMYAPP IRGSINCVSNITGILLTRDGGTNMSNETFRPGGGNIKDNWRSELYKYKVVEIEPLGIAP TKCKRRVV AVGIGAMSFGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQ HLLQDTHWGIKQLQARVLAVEHYLKDQKFLGLWGCSGKIICCTAVPWNSTWSNRS YEEIWDNMTWINWSREISNYTSQIYEILTESQNQQDRNNKSLLEDL double underlined amino acids are glycan mutations CNE55_HM215418_MD39_L14G8 MDWTWILFLVAAATRVHSSDKLWVTVVYGVPVWRDADTTLFCASDAKAH ETEVHNVWATHACVPTDPNPQEIHLVNVTENFNMWKNKMVEQMQEDVISLWDESL KPCVKLTPLCVTLNCTTANTNETKNNTTDDNIKDEMKNCTFNMTTEIRDKKQRVSA LFYKLDIVPIDDSKNNSEYRLINCNTSVIKQACPKVSFDPIPIHYCTPAGYVILKCNDK NFNGTGPCKNVSSVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNAKNIIVHLNK SVEINCTRPSNNTVTSVRIGPGQVFYYTGDITGDIRKAYCEIDGTEWNKTLTQVAEKL KEHFNKTIVYQPPSGGDLEITMHHFNCRGEFFYCNTTQLFNNSVGNSTIKLPCRIKQII NMWQGVGQAMYAPPISGAINCLSNITGILLTRDGGGNNRSNETFRPGGGNIKDNWRS ELYKYKVVEIEPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGIGAMSFGFLGAAGS TMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHMLQDTHWGIKQLQARVLAVE HYLKDQRFLGLWGCSGKTICCTAVPWNSTWSNKTYEEIWDNMTWTNWSREISNYT NQIYSILTESQSQQDKNNKSLLELD Sequence in bold is the IgE leader sequence; underlined  sequence is the linker sequence; double underlined  amino acids are glycan mutations SDKLWVTVYYGVPVWRDADTTLFCASDAKAHETEVHNVWATHACVPTDPN PQEIHLVNVTENFNMWKNKMVEQMQEDVISLWDESLKPCVKLTPLCVTLNCTTANT NETKNNTTDDNIKDEMKNCTFNMTTEIRDKKQRVSALFYKLDIVPIDDSKNNSEYRLI NCNTSVIKQACPKVSFDPIPIHYCTPAGYVILKCNDKNFNGTGPCKNVSSVQCTHGIK PVVSTQLLLNGSLAEEEIIIRSENLTDNAKNIIVHLNKSVEINCTRPSNNTVTSVRIGPG QVFYYTGDITGDIRKAYCEIDGTEWNKTLTQVAEKLKEHFNKTIVYQPPSGGDLEIT MHHFNCRGEFFYCNTTQLFNNSVGNSTIKLPCRIKQIINMWQGVGQAMYAPPISGAI NCLSNITGILLTRDGGGNNRSNETFRPGGGNIKDNWRSELYKYKVVEIEPLGIAPTKC KRRVV AVGIGAMSFGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQ HMLQDTHWGIKQLQARVLAVEHYLKDQRFLGLWGCSGKTICCTAVPWNSTWSNKT YEEIWDNMTWTNWSREISNYTNQIYSILTESQSQQDKNNKSLLELD double underlined amino acids are glycan mutations AD8_MD64_link14_TS1 MDWTWILFLVAAATRVHIVENLWVTVYYGVPVWKEATTTLFCASDAKAY DTEVHNVEATHECVPTDPNPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSL KPCVKLTPLCVTLNCTDLRNVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFY RLDVVPIDNDNTSYRLINCNTSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGT GPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKKESVEIN CTRPNNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFG NNKTIVFNQSSGGDPEIVMHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEG NDTITLPCRIKQIINMWQEVGKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETF RPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAV GTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLT VWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWN

QEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLRN VTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINCN TSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVVS TQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNTVKSIHIGPGRAFY YTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMHS FNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEVG KAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKYK VVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMGA ASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLRD QQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIYT LIEESQNQQEKNEQELLELD Sequence in bold is the IgE leader sequence; underlined  sequences are the linker sequences; italicized sequences  are repeat 1 optimized for human; dotted underlined sequences are repeat 2 optimized for human/mouse;  double underlined sequences are repeat 3 optimized for mouse to prevent recombination and large  repeats on the nucleic acid level Repeat 1 of SEQ ID NO: (above)-optimized for human VENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDPN PQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLR NVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINC NTSTITQACPKVSFEPIPIHYCTPAGFAILCKDKKFNGTGPCKNVSTVQCTHGIRPVV STQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNNTVKSIHIGPGRAF YYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMH SFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEV GKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKY KVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMG AASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLR DQQLLGIQGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIY TLIEESQNQQEKNEQELLELD Underlined sequences is a linker Repeat 2 of SEQ ID NO: (above)-optimized for human/mouse VENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDPN PQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLR NVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINC NTSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVV STQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNNTVKSIHIGPGRAF YYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMH SFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEV GKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKY KVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMG AASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLR DQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIY TLIEESQNQQEKNEQELLELD Underlined sequences is a linker Repeat 3 of SEQ ID NO: (above)-optimized for mouse  to prevent recombination and large repeats on the nucleic acid level VENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDPN PQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLR NVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINC NTSTITQACPKVSFEPIPHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVV STQLLLNGSLAEEEVIIRSSNFTDNAKVIIVQLKESVEINCTRPNNNTVKSIHIGPGRAF YYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMH SFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEV GKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKY KVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMG AASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLR DQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIY TLIEESQNQQEKNEQELLELD Underlined sequences is a linker AD8_MD64_link14 MDWTWILFLVAAATRVHIVEENLWVTVYYGVPVWKEATTTLFCASDAKAY DTEVHNVWATHECVPTDPNPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSL KPCVKLTPLCVTLNCTDLRNVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFY RLDVVPIDNDNTSYRLINCNTSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGT GPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEIN CTRPNNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFG NNKTIVFNQSSGGDPEIVMHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEG NDTITLPCRIKQIINMWQEVGKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETF RPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAV GTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLT VWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWN NMTWMEWEREIDNYTGLIYTLIEESQNQQEKNEQELLELD sequence in bold is the IgE leader sequence;  underlined sequence is a linker sequence VENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDPN PQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLR NVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINC NTSTITQACPKVSFEPIPHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVV STQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNNTVKSIHIGPGRAF YYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMH SFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEV GKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKY KVVKIEPLGVAPTKCKRRVVQ AVGTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQ QHLLQLTVWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNK TLDMIWNNMTWMEWEREIDNYTGLIYTLIEESQNQQEKNEQELLELD 001428_MD39_link14_TS1 MDWTWILFLVAAATRVHIVENLWVTVYYGVPVWKEARTTLFCASDAKAY ETEVHNVWATHACVPTDPNPQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQ SLKPCVKLTPLCVTLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQ KAYALFYRLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAG YAILKCNNKTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNV KTIIVHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEM LRRVSEKLAEHFPNKTIKFTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTY MPNGTNNSNSTIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGK NNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGS GGHAAVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQ HLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSL

THACVPTDPNPQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAOSLKPCVKLTP LCVTLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRL DLVPLERENRGDSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNK TFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQS VEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAE HFPNKTIKFTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSN STIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPG GGDMRDNWRSELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLG AVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGI KQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTW MQWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALD Sequence in bold is the IgE leader sequence;  underlined sequences are the linker sequences; italicized sequences are repeat 1  optimized for human; dotted underlined sequences are repeat 2 optimized for human/ mouse; double underlined sequences are repeat 3 optimized for mouse to prevent recombination and  large repeats on the nucleic acid level Repeat 1 of SEQ ID NO: (above)-optimized for human VENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDPN PQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQV NATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRG DSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNKTFNGTGSCNNV STVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNN TVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTS SSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQII NMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGMRDNWRS ELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAG STMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRVLAIE HYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWMQWDREVSNY TGIIYRLLEDSQNQQERNEQDLLALD Repeat 2 of SEQ ID NO: (above)-optimized for human/mouse VENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNWATHACVPTDPN PQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQV NATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQDAYALFYRLDLVPLERENRG DSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNKTFNGTGSCNNV STVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNN TVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTS SSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQII NMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRS ELKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAG STMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRVLAIE HYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWMQWDREVSNY TGIIYRLLEDSQNQQERNEQDLLALD Repeat 3 of SEQ ID NO: (above)-optimized for mouse  to prevent recombination and large repeats on the nucleic acid level during DNA replication. VENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDPN PQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQV NATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRG DSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNKTGNGTGSCNNV STVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNN TVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTS SSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQII NMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRS ELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAG STMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRVLAIE HYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWMQWDREVSNY TGIIYRLLEDSQNQQERNEQDLLALD 001428_MD39_link14_pVax MDWTWILFLVAAATRVHIVENLWVTVYYGVPVWKEARTTLFCASDAKAY ETEVHNVWATHACVPTDPNPQEMVLGNVTENFNMWKNDMVSQMHEDVISLWAQ SLKPCVKLTPLCVTLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQ KAYALFYRLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAG YAILKCNNKTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGLSAEEEIIIRSENLTDNV KTIIVHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEM LRRVSEKLAEHFPNKTIKFTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTY MPNGTNNSNSTIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGK NNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGS GGHAAVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQ HLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSL TDIWDNMTWMQWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALD Sequence in bold is an IgE leader sequence; underlined  sequence is a linker sequence VENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDPN PQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQV NATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRG DSNSASKYILINCNTSAITQACPKVNFDPIPHYCTPAGYAILKCNNKTFNGTGSCNNV STVQCTHGIKPVVSTLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNN TVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTS SSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQII NMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRS ELYKYKVVEIKPLGVAPTRCKRRVV AVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQ HLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSL TDIWDNMTWMQWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALD In some embodiments, the expressible nucleic acid sequence  comprises a nucleic acid sequence encoding a trimer peptide, wherein the nuceic acid sequence comprises  any one or more of the following sequences or a sequence that comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the following sequences: BG505_SOSIP_MD39-nucleic acid ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTCTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAjGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCCGGCGCAGGAGACGGCGCGCAGTGGGCATCGGGCCGTGTC CCTGGGCTTTCTGGGAGCAGCAGGCTCCACAATGGGAGCAGCCTCTATGACCCTG ACAGTGCAGGCCAGGAATCTGCTGAGCGGCATCGTGCAGCAGCAGTCCAACCTG CTGAGAGCCCCAGAGCCCCAGCAGCACCTGCTGAAGGACACCCACTGGGGCATC AAGCAGCTGCAGGCCAGGGTGCTGGCAGTGGAGCACTATCTGAGAGATCAGCAG CTGCTGGGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACCAATGTGCCCT GGAACTCTAGCTGGTCTAATCGCAACCTGAGCGAGATCTGGGACAATATGACCT GGCTGCAGTGGGATAAGGAGATCTCCAACTACACACAGATCATCTATGGCCTGCT GGAAGAATCTCAGAATCAGCAGGAAAAGAATGACCAGGATCTGCTGGCACTGGA TTGATAACTCGAG BG505_MD39_GRSF (Glycan)-nucleic acid ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCCGGCGCAGGAGACGGCGCGCAGTGGGCATCGGAGCCGTGTC CCTGGGCTTTCTGGGAGCAGCAGGCTCCACAATGGGAGCAGCCTCTATGACCCTG ACAGTGCAGGCCAGGAATCTGCTGAGCGGCATCGTGCAGCAGCAGTCCAACCTG CTGAGAGCCCCAGAGCCCCAGCAGCACCTGCTGAAGGACACCCACTGGGGCATC AAGCAGCTGCAGGCCAGGGTGCTGGCAGTGGAGCACTATCTGAGAGATCAGCAG CTGCTGGGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACCAATGTGCCCT GGAACTCTAGCTGGTCTAATCGCAACCTGAGCGAGATCTGGGACAATATGACCT GGCTGAACTGGAGCAAGGAGATCTCCAACTACACACAGATCATCTATGGCCTGC TGGAAGAATCTCAGAATCAGCAGGAAAAGAATAACCAGAGCCTGCTGGCACTGG ATTGATAA B505_SOSIP_MD39_CPG9.2-nucleic acid ATGGATTGGACTTGGATTCTGTTCCTGGTCGCAGCAGCCACACGAGTGCAT AGCGGGGGAAATAGTAGCGGCAGCCTGGGGTTCCTGGGAGCAGCAGGCTCCACC ATGGGAGCAGCATCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGTCTGGC ATCGTGCAGCAGCAGAGCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCTG CTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCCGGGTGCTGGCAGTG GAGCACTACCTGCGCGATCAGCAGCTGCTGGGAATCTGGGGATGCAGCGGCAAG CTGATCTGCTGTACAAATGTGCCTTGGAACAGCTCCTGGTCCAATAGGAACCTGT CTGAGATCTGGGACAATATGACCTGGCTGAACTGGTCTAAGGAGATCAGCAATT ACACACAGATCATCTATGGCCTGCTGGAGGAGAGCCAGAATCAGAACGAGTCCA ATGAGCAGGATCTGGGCGGCAACGGCAGCGGCGGCGGCAGCGGCTCCGGCGGC AACGGCTCTAGCGGCCTGTGGGTGACCGTGTACTATGGCGTGCCCGTGTGGAAG GACGCCGAGACTACGCTGTTCTGCGCCTCCGATGCCAAGGCCTATGAGACAGAG AAGCACAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCTAACCCACAG GAGATCCACCTGGAGAATGTGACCGAGGAGTTTAACATGTGGAAGAACAATATG GTGGAGCAGATGCACGAGGACATCATCAGCCTGTGGGATCAGTCCCTGAAGCCT TGCGTGAAGCTGACCCCACTGTGCGTGACACTGCAGTGTACCAACGTGACAAAC AATATCACCGACGATATGAGGGGCGAGCTGAAGAATTGTTCTTTCAACATGACC ACAGAGCTGAGGGACAAGAAGCAGAAAGTGTACAGCCTGTTTTATAGACTGGAT GTGGTGCAGATCAATGAGAACCAGGGCAATAGGAGCAACAATTCCAACAAGGA GTACAGACTGATCAATTGCAACACCAGCGCCATCACACAGGCCTGTCCAAAGGT GTCCTTCGAGCCCATCCCTATCCACTATTGCGCACCAGCAGGATTCGCAATCCTG AAGTGTAAGGATAAGAAGTTTAACGGAACCGGACCATGCCCATCTGTGAGCACC GTGCAGTGTACACACGGCATCAAGCCAGTGGTGTCCACACAGCTGCTGCTGAAT GGCTCTCTGGCCGAGGAGGAAGTGATCATCCGGAGCGAGAACATCACCAACAAT GCCAAGAATATCCTGGTGCAGCTGAACACACCCGTGCAGATCAATTGCACCCGG CCTAACAATAACACAGTGAAGTCCATCAGGATCGGACCAGGACAGGCCTTTTAC TATACCGGCGACATCATCGGCGATATCCGCCAGGCCCACTGTAACGTGAGCAAG GCCACCTGGAACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTC GGCAATAACACCATCATCAGATTTGCACAGTCCTCTGGCGGCGACCTGGAGGTG ACCACACACTCCTTCAACTGCGGCGGCGAGTTCTTTTACTGTAACACATCTGGCC TGTTTAATAGCACCTGGATCTCTAACACAAGCGTGCAGGGCTCCAATTCTACCGG CTCCAACGATTCTATCACACTGCCCTGCCGGATCAAGCAGATCATCAACATGTGG CAGAGGATCGGACAGGCAATGTACGCCCCTCCCATCCAGGGCGTGATCAGATGC GTGAGCAATATCACCGGCCTGATCCTGACACGCGACGGCGGCAGCACCAACTCC ACCACAGAGACATTCAGACCCGGCGGCGGCGACATGAGGGATAACTGGAGATCC GAGCTGTATAAGTATAAAGTCGTGAAGATTGAGCCACTGGGCGTCGCACCAACA AGATGTAATAGAAGCTGATAA BG505_SOSIP_MD39_link14-nucleic acid ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATTGATAA BG505_SOSIP_MD39_trimer string 1 (TS1)-nucleic acid ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATGGCGGCGCCGAAAACCTGTGGGTCACC GTGTACTACGGAGTCCCCGTGTGGAAAGATGCAGAGACAACCCTGTTCTGCGCTT CCGACGCTAAAGCTTACGAGACAGAAAAACACAACGTGTGGGCCACTCATGCCT GCGTGCCTACAGACCCTAACCCACAGGAAATCCACCTGGAGAATGTGACGGAGG AGTTTAACATGTGGAAGAATAACATGGTCGAGCAGATGCATGAAGATATCATTT CCTTATGGGACCAATCCCTGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGAC ACTGCAATGCACTAACGTGACCAATAACATTACCGACGATATGCGCGGCGAAGCT GAAGAACTGCTCTTTCAACATGACTACCGAGCTGAGAGATAAGAAACAGAAAGT GTACAGCCTGTTTTATCGGTTAGATGTGGTGCAGATCAATGAAAACCAGGGCAAT CGGTCCAACAATTCTAACAAGGAATATCGCCTGATCAATTGTAACCCTCCGCCA TTACCCAGGCTTGCCCTAAGGTGTCTTTCGAGCCCATCCCTATCCACTATTGCGCC CCAGCTGGATTTGCTATCCTGAAGTGTAAGGACAAAAAGTTTAACGGGACCGGA CCATGTCCTAGCGTGTCCACTGTGCAGTGCACCCATGGCATCAAGCCTGTGGTGT CCACCCAACTTCTGCTGAATGGCTCTCTGGCTGAAGAAGAAGTGATCATTAGGTC CGAAAATATTACTAATAACGCTAAAAATATCCTGGTCCAGCTGAACACGCCTGTC CAGATCAATTGTACCCGGCCAAATAACAACACAGTGAAGTCTATCAGAATCGGC CCAGGCCAGGCCTTCTACTACACAGGCGACATTATCGGCGATATTCGCCAGGCCC ACTGTAATGTGAGCAAAGCTACATGGAATGAGACACTGGGCAAGGTAGTCAAAC AGCTGAGAAAACATTTTGGAAACAACACCATCATCCGCTTTGCACAGTCTAGCGG CGGCGACCTGGAGGTAACTACCCACAGCTTCAATTGTGGCGGCGAGTTCTTTTAC TGTAATACCAGCGGCCTGTTTAATAGTACTTGGATCAGCAACACATCTGTGCAGG GCTCTAACTCCACTGGCTCTAACGATAGCATCACACTGCCTTGTCGGATCAAGCA AATCATCAACATGTGGCAAAGGATTGGGCAGGCTATGTATGCCCCTCCAATCCAG GGCGTGATCCGGTGCGTGAGCAACATTACAGGCCTGATCCTGACAAGAGACGGC GGCTCCACCAACTCTACTACCGAGACATTCCGGCCCGGCGGCGGCGACATGCGT GATAACTGGCGCAGCGAACTGTATAAATATAAAGTGGTGAAGATCGAGCCTCTG GGCGTGGCCCCAACTAGGTGTAAAAGAAGGGTCGTCGGCTCCCACAGCGGCAGC GGCGGCTCCGGCTCTGGCGGCCACGCGGCTGTCGGCATCGGCGCCGTGAGCCTG GGCTTTCTGGGCGCCGCCGGCTCCACTATGGGCGCAGCCTCTATGACCCTGACTG TCCAGGCTAGAAATCTGCTGTCTGGAATCGTGCAGCAGCAGTCTAACCTGCTGAG GGCACCTGAGCCACAACAGCACCTGCTGAAGGATACACATTGGGGCATCAAGCA GTTACAAGCCAGGGTGCTGGCCGTGGAACACTACCTGCGCGATCAGCAATTACT GGGCATTTGGGGATGCTCTGGCAAGCTGATTTGTTGCACCAATGTGCCCTGGAAC TCCTCTTGGAGCAACAGAAACCTGTCCGAAATCTGGGATAACATGACATGGCTGC AGTGGGACAAGGAAATTTCCAATTATACCCAGATCATCTATGGACTGCTGGAAG AAAGTCAGAATCAGCAGGAGAAGAATGAACAGGATCTGCTGGCACTGGATGGCG GCGCCGAAAACCTGTGGGTCACCGTGTATTATGGAGTGCCAGTGTGGAAGGACG CCGAGACCACACTGTTTTGTGCCTCTGATGCCAAGGCCTACGAGACCGAGAAGC ACAACGTGTGGGCCACCCACGCCTGCGTGCCCACAGACCCAAATCCTCAGGAGA TCCACCTGGAGAACGTGACCGAGGAGTTTAACATGTGGAAGAACAATATGGTGG AGCAGATGCACGAGGATATCATCTCTCTGTGGGATCAGTCTCTGAAGCCATGTGT GAAGCTGACCCCACTGTGCGTGACCCTGCAGTGTACAAATGTGACAAACAACAT CACAGATGACATGAGAGGCGAGCTGAAGAACTGTTCCTTCAATATGACCACCGA GCTGAGAGACAAGAAGCAGAAGGTGTATTCTCTGTTTTACCGGCTGGACGTGGT GCAGATCAACGAGAATCAAGGGCAATCGGTCTAACAACTCCAATAAGGAGTATAG ACTGATCAACTGCAACACCTCTGCCATCACCCAGGCCTGTCCTAAGGTGTCCTTT GAGCCAATCCCAATCCACTATTGCGCCCCTGCCGGCTTTGCCATCCTGAAGTGCA AGGACAAGAAGTTTAACGGCACAGGCCCCTGCCCATCCGTGAGCACAGTGCAGT GTACCCACGGCATCAAGCCTGTGGTGTCCACCCAGCTGCTGCTGAACGGCTCCCT GGCCGAGGAGGAGGTAATCATCAGGTCTGAGAACATCACAAATAACGCCAAGAA CATCCTGGTGCAGCTGAACACCCCAGTGCAGATCAACTGTACCCGGCCTAACAAT AATACCGTGAAGTCTATCCGGATCGGCCCAGGCCAGGCCTTCTACTATACCGGCG ATATCATCGGCGATATCAGACAGGCCCACTGCAACGTGTCCAAGGCCACATGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGCGGAAGCACTTTGGCAATAACA CCATCATCAGATTCGCCCAGTCTTCCGGCGGCGACCTGGAGGTGACAACCCACTC CTTCAATTGCGGCGGCGAGTTCTTTTACTGTAATACAAGCGGCCTGTTTAATAGC ACCTGGATCTCTAACACCTCCGTGCAGGGCTCCACAGCACAGGCTCTAATGATT CCATCACCCTGCCTTGCCGGATCAAGCAGATCATCAATATGTGGCAGAGAATCGG CCAGGCCATGTATGCCCCTCCAATCCAGGGCGTGATCCGCTGCGTGTCCAACATC ACAGGCCTGATCCTGACAAGAGATGGCGGCTCCACCAACAGCACCACAGAGACC TTCAGACCCGGCGGCGGCGACATGCGCGACAACTGGAGATCCGAGCTGTATAAG TACAAGGTGGTGAAGATCGAGCCCCTGGGCGTGGCCCCAACCCGGTGTAAGCGC AGAGTGGTGGGCAGCCACAGCGGCAGCGGCGGCAGCGGCTCCGGCGGCCACGCC GCCGTGGGCATCGGCGCCGTGTCCCTGGGCTTCCTGGGCGCCGCCGGCTCCACCA TGGGCGCCGCCTCCATGACACTGACAGTGCAGGCCAGAAATCTGCTGTCCGGCAT CGTGCAGCAGCAGTCCAATCTGCTGCGGGCCCCTGAGCCACAGCAGCACCTGCT GAAGGATACCCACTGGGGCATCAAGCAGCTGCAGGCCCGGGTGCTGGCCGTGGA GCACTACCTGAGGGATCAGCAGCTGCTGGGCATCTGGGGCTGTTCCGGCAAGCT GATCTGCTGTACAAACGTGCCCTGGAACAGCTCCTGGTCCAATAGGAACCTGTCC GAGATCTGGGATAACATGACCTGGCTGCAGTGGGATAAGGAGATCAGCAACTAC ACACAGATCATCTACGGCCTGCTGGAGGAGAGCCAGAATCAGCAGGAGAAGAAC GAGCAGGACCTGCTGGCCCTGGAT BG505_SOSIP_MD39_trimer string 2 (TS2) ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCTCTGGGGCTGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATggcggcagcggcagcggcGCCGAAAACCTGTGG GTCACCGTGTACTACGGAGTCCCCGTGTGGAAAGATGCAGAGACAACCCTGTTCT GCGCTTCCGACGCTAAAGCTTACGAGACAGAAAAACACAACGTGTGGGCCACTC ATGCCTGCGTGCCTACAGACCCTAACCCACAGGAAATCCACCTGGAGAATGTGA CGGAGGAGTTTAACATGTGGAAGAATAACATGGTCGAGCAGATGCATGAAGAT TCATTTCCTTATGGGACCAATCCCTGAAGCCTTGCGTGAAGCTGACCCCACTGTG CGTGACACTGCAATGCACTAACGTGACCAATAACATTACCGACGATATGCGCGG CGAGCTGAAGAACTGCTCTTTCAACATGACTACCGAGCTGAGAGATAAGAAACA GAAAGTGTACAGCCTGTTTTATCGGTTAGATGTGGTGCAGATCAATGAAAACCAG GGCAATCGGTCCAACAATTCTAACAAGGAATATCGCCTGATCAATTGTAACACCT CCGCCATTACCCAGGCTTGCCCTAAGGTGTCTTTCGAGCCCATCCCTATCCACTAT TGCGCCCCAGCTGGATTTGCTATCCTGAAGTGTAAGGACAAAAAGTTTAACGGG ACCGGACCATGTCCTAGCGTGTCCACTGTGCAGTGCACCCATGGCATCAAGCCTG TGGTGTCCACCCAACTTCTGCTGAATGGCTCTCTGGCTGAAGAAGAAGTGATCAT TAGGTCCGAAAATATTACTAATAACGCTAAAAATATCCTGGTCCAGCTGAACACG CCTGTCCAGATCAATTGTACCCGGCCAAATAACAACACAGTGAAGTCTATCAGA ATCGGCCCAGGCCAGGCCTTCTACTACACAGGCGACATTATCGGCGATATTCGCC AGGCCCACTGTAATGTGAGCAAAGCTACATGGAATGAGACACTGGGCAAGGTAG TCAAACAGCTGAGAAAACATTTTGGAAACAACACCATCATCCGCTTTGCACAGTC TAGCGGCGGCGACCTGGAGGTAACTACCCACAGCTTCAATTGTGGCGGCGAGTT CTTTTACTGTAATACCAGCGGCCTGTTTAATAGTACTTGGATCAGCAACACATCT GTGCAGGGCTCTAACTCCACTGGCTCTAACGATAGCATCACACTGCCTTGTCGGA TCAAGCAAATCATCAACATGTGGCAAAGGATTGGGCAGGCTATGTATGCCCCTCC AATCCAGGGCGTGATCCGGTGCGTGAGCAACATTACAGGCCTGATCCTGACAAG AGACGGCGGCTCCACCAACTCTACTACCGAGACATTCCGGCCCGGCGGCGGCGA CATGCGTGATAACTGGCGCAGCGAACTGTATAAATATAAAGTGGTGAAGATCGA GCCTCTGGGCGTGGCCCCAACTACCTGTAAAAGAAGGGTCGTCGGCTCCCACAG CGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCGGCTGTCGGCATCGGCGCCGT GAGCCTGGGCTTTCTGGGCGCCGCCGGCTCCACTATGGGCGCAGCCTCTATGACC CTGACTGTCCAGGCTAGAAATCTGCTGTCTGGAATCGTGCAGCAGCAGTCTAACC TGCTGAGGGCACCTGAGCCACAACAGCACCTGCTGAAGGATACACATTGGGGCA TCAAGCAGTTACAAGCCAGGGTGCTGGCCGTGGAACACTACCTGCGCGATCAGC AATTACTGGGCATTTGGGGATGCTCTGGCAAGCTGATTTGTTGCACCAATGTGCC CTGGAACTCCTCTTGGAGCAACAGAAACCTGTCCGAAATCTGGGATAACATGAC ATGGCTGCAGTGGGACAAGGAAATTTCCAATTATACCCAGATCATCTATGGACTG CTGGAAGAAAGTCAGAATCAGCAGGAGAAGAATGAACAGGATCTGCTGGCACTG GATggcggcagcggcagcggcGCCGAAAACCTGTGGGTCACCGTGTATTATGGAGTGCCA GTGTGGAAGGACGCCGAGACCACACTGTTTTGTGCCTCTGATGCCAAGGCCTACG AGACCGAGAAGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACAGACCCAA ATCCTCAGGAGATCCACCTGGAGAACGTGACCGAGGAGTTTAACATGTGGAAGA ACAATATGGTGGAGCAGATGCACGAGGATATCATCTCTCTGTGGGATCAGTCTCT GAAGCCATGTGTGAAGCTGACCCCACTGTGCGTGACCCTGCAGTGTACAAATGTG ACAAACAACATCACAGATGACATGAGAGGCGAGCTGAAGAACTGTTCCTTCAAT ATGACCACCGAGCTGAGAGACAAGAAGCAGAAGGTGTATTCTCTGTTTTACCGG CTGGACGTGGTGCAGATCAACGAGAATCAGGGCAATCGGTCTAACAACTCCAAT AAGGAGTATAGACTGATCAACTGCAACACCTCTGCCATCACCCAGGCCTGTCCTA AGGTGTCCTTTGAGCCAATCCCAATCCACTATTGCGCCCCTGCCGGCTTTGCCATC CTGAAGTGCAAGGACAAGAAGTTTAACGGCACAGGCCCCTGCCCATCCGTGAGC ACAGTGCAGTGTACCCACGGCATCAAGCCTGTGGTGTCCACCCAGCTGCTGCTGA ACGGCTCCCTGGCCGAGGAGGAGGTAATCATCAGGTCTGAGAACATCACAAATA ACGCCAAGAACATCCTGGTGCAGCTGAACACCCCAGTGCAGATCAACTGTACC GGCCTAACAATAATACCGTGAAGTCTATCCGGATCGGCCCAGGCCAGGCCTTCTA CTATACCGGCGATATCATCGGCGATATCAGACAGGCCCACTGCAACGTGTCCAA GGCCACATGGAACGAGACACTGGGCAAGGTGGTGAAGCAGCTGCGGAAGCACTT TGGCAATAACACCATCATCAGATTCGCCCAGTCTTCCGGCGGCGACCTGGAGGTG ACAACCCACTCCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAATACAAGCGGCC TGTTTAATAGCACCTGGATCTCTAACACCTCCGTGCAGGGCTCCAACAGCACAGG CTCTAATGATTCCATCACCCTGCCTTGCCGGATCAAGCAGATCATCAATATGTGG CAGAGAATCGGCCAGGCCATGTATGCCCCTCCAATCCAGGGCGTGATCCGCTGC GTGTCCAACATCACAGGCCTGATCCTGACAAGAGATGGCGGCTCCACCAACAGC ACCACAGAGACCTTCAGACCCGGCGGCGGCGACATGCGCGACAACTGGAGTCC GAGCTGTATAAGTACAAGGTGGTGAAGATCGAGCCCCTGGGCGTGGCCCCAACC CGGTGTAAGCGCAGAGTGGTGGGCAGCCACAGCGGCAGCGGCGGCAGCGGCTCC GGCGGCCACGCCGCCGTGGGCATCGGCGCCGTGTCCCTGGGCTTCCTGGGCGCCG CCGGCTCCACCATGGGCGCCGCCTCCATGACACTGACAGTGCAGGCCAGAAATC TGCTGTCCGGCATCGTGCAGCAGCAGTCCAATCTGCTGCGGGCCCCTGAGCCACA GCAGCACCTGCTGAAGGATACCCACTGGGGCATCAAGCAGCTGCAGGCCCGGGT GCTGGCCGTGGAGCACTACCTGAGGGATCAGCAGCTGCTGGGCATCTGGGGCTG TTCCGGCAAGCTGATCTGCTGTACAAACGTGCCCTGGAACAGCTCCTGGTCCAAT AGGAACCTGTCCGAGATCTGGGATAACATGACCTGGCTGCAAGTGGGATAAGGAG ATCAGCAACTACACACAGATCATCTACGGCCTGCTGGAGGAGAGCCAGAATCAG CAGGAGAAGAACGAGCAGGACCTGCTGGCCCTGGATTGATAA BG505_MD39_link14_gp140-PDGFR ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATGGAGGAGGAAGCGGGGGAAGCGGGGG AAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAACGCCGTGGGCCAGGACACCC AGGAAGTGATCGTGGTGCCCCACAGCCTGCCTTTCAAGGTGGTGGTCATCTCCGC CATCCTGGCCCTGGTCGTGCTGACTATTATTTCCCTGATTATCCTGATTATGCTGT GGCAGAAGAAGCCCAGATGATAA BG505_MD39_gp140_foldon-PDGFR ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTCTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTCGCTTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGGGCTGGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATGGAGGAGGAAGCGGGGGAAGCGGCGG CGGCTACATCCCTGAGGCCCCAAGGGACGGACAGGCCTATGTGAGAAAGGATGG CGAGTGGGTGCTGCTGTCCACCTTCCTGGGGGAAGCGGAGGAAGCGGGGGAAG CGGGGGAAGCAACGCCGTGGGCCAGGACACCCAGGAAGTGATCGTGGTGCCCCA CAGCCTGCCTTTCAAGGTGGTGGTCATCTCCGCCATCCTGGCCCTGGTCGTGCTG ACTATTATTTCCCTGATTATCCTGATTATGCTGTGGCAGAAGAAGCCCAGATGAT AA BG505_MD39_TS1_gp140-PDGFR ATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCTACAAGAGTGCAT TCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACGAGACAGAGAAG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAAACCCCCAGGAG ATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGAACAATATGGTG GAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCCTGCG TGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTGACAAACAATAT CACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAACATGACCACAGA GCTGAGGGACAAGAAGCAGAAGGTGTACTCCCTGTTTTATAGACTGGATGTGGT GCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAACAAGGAGTACCG CCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTAAGGTGTCTTTC GAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTA AGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCTACCGTGCAGTG TACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTG GCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACAATGCCAAGAAT ATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCCGGCCCAACAAT AACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTACTATACCGGCG ACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAAGGCCACCTGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTTCGGCAATAACA CCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGTGACCACACACT CCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGCCTGTTTAATTCC ACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCGGCAGCAACGATT CCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGTGGCAGCGCATCG GCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGATGCGTGAGCAATAT CACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACAGCACCACAGAGAC ATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAA GTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAACCAGGTGCAAGAG GAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGC CGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCCAC AATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGAATCTGCTGAGCGG CATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGCCCCAGCAGCACCT GCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGT GGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAA GCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTCTAATCGCAACCTG AGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAAGGAGATCTCCAAC TACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAATCAGCAGGAAAAG AATGAACAGGATCTGCTGGCACTGGATGGCGGCGCCGAAAACCTGTGGGTCACC GTGTACTACGGAGTCCCCGTGTGGAAAGATGCAGAGACAACCCTGTTCTGCGCTT CCGACGCTAAAGCTTACGAGACAGAAAAACACAACGTGTGGGCCACTCATGCCT GCGTGCCTACAGACCCTAACCCACAGGAAATCCACCTGGAGAATGTGACGGAGG AGTTTAACATGTGGAAGAATAACATGGTCGAGCAGATGCATGAAGATATCATTT CCTTATGGGACCAATCCCTGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGAC ACTGCAATGCACTAACGTGACCAATAACATTACCGACGATATGCGCGGCGAGCT GAAGAACTGCTCTTTCAACATGACTACCGAGCTGAGAGATAAGAAACAGAAAGT GTACAGCCTGTTTTATCGGTTAGATGTGGTGCAGATCAATGAAAACCAGGGCAAT CGGTCCAACAATTCTAACAAGGAATATCGCCTGATCAATTGTAACACCTCCGCCA TTACCCAGGCTTGCCCTAAGGTGTCTTTCGAGCCCATCCCTATCCACTATTGCGCC CCAGCTGGATTTGCTATCCTGAAGTGTAAGGACAAAAGTTTAACGGGACCGGA CCATGTCCTAGCGTGTCCACTGTGCAGTGCACCCATGGCATCAAGCCTGTGGTGT CCACCCAACTTCTGCTGAATGGCTCTCTGGCTGAAGAAGAAGTGATCATTAGGTC CGAAAATATTACTAATAACGCTAAAAATATCCTGGTCCAGCTGAACACGCCTGTC CAGATCAATTGTACCCGGCCAAATAACAACACAGTGAAGTCTATCAGAATCGGC CCAGGCCAGGCCTTCTACTACACAGGCGACATTATCGGCGATATTCGCCAGGCCC ACTGTAATGTGAGCAAAGCTACATGGAATGAGACACTGGGCAAGGTAGTCAAAC AGCTGAGAAAACATTTTGGAAACAACACCATCATCCGCTTTGCACAGTCTAGCGG CGGCGACCTGGAGGTAACTACCCACAGCTTCAATTGTGGCGGCGAGTTCTTTTAC TGTAATACCAGCGGCCTGTTTAATAGTACTTGGATCAGCAACACATCTGTGCAGG GCTCTAACTCCACTGGCTCTAACGATAGCATCACACTGCCTTGTCGGATCAAGCA AATCATCAACATGTGGCAAAGGATTGGGCAGGCTATGTATGCCCCTCCAATCCAG GGCGTGATCCGGTGCGTGAGCAACATTACAGGCCTGATCCTGACAAGAGACGGC GGCTCCACCAACTCTACTACCGAGACATTCCGGCCCGGCGGCGGCGACATGCGT GATAACTGGCGCAGCGAACTGTATAAATATAAAGTGGTGAAGATCGAGCCTCTG GGCGTGGCCCCAACTAGGTGTAAAAGAAGGGTCGTCGGCTCCCACAGCGGCAGC GGCGGCTCCGGCTCTGGCGGCCACGCGGCTGTCGGCATCGGCGCCGTGAGCCTG GGCTTTCTGGGCGCCGCCGGCTCCACTATGGGCGCAGCCTCTATGACCCTGACTG TCCAGGCTAGAAATCTGCTGTCTGGAATCGTGCAGCAGCAGTCTAACCTGCTGAG GGCACCTGAGCCACAACAGCACCTGCTGAAGGATACACATTGGGGCATCAAGCA GTTACAAGCCAGGGTGCTGGCCGTGGAACACTACCTGCGCGATCAGCAATTACT GGGCATTTGGGGATGCTCTGGCAAGCTGATTTGTTGCACCAATGTGCCCTGGAAC TCCTCTTGGAGCAACAGAAACCTGTCCGAAATCTGGGATAACATGACATGGCTGC AGTGGGACAAGGAAATTTCCAATTATACCCAGATCATCTATGGACTGCTGGAAG AAAGTCAGAATCAGCAGGAGAAGAATGAACAGGATCTGCTGGCACTGGATGGCG GCGCCGAAAACCTGTGGGTCACCGTGTATTATGGAGTGCCAGTGTGGAAGGACG CCGAGACCACACTGTTTTGTGCCTCTGATGCCAAGGCCTACGAGACCGAGAAGC ACAACGTGTGGGCCACCCACGCCTGCGTGCCCACAGACCCAAATCCTCAGGAGA TCCACCTGGAGAACGTGACCGAGGAGTTTAACATGTGGAAGAACAATATGGTGG AGCAGATGCACGAGGATATCATCTCTCTGTGGGATCAGTCTCTGAAGCCATGTGT GAAGCTGACCCCACTGTGCGTGACCCTGCAGTGTACAAATGTGACAAACAACAT CACAGATGACATGAGAGGCGAGCTGAAGAACTGTTCCTTCAATATGACCACCGA GCTGAGAGACAAGAAGCAGAAGGTGTATTCTCTGTTTTACCGGCTGGACGTGGT GCAGATCAACGAGAATCAGGGCAATCGGTCTAACAACTCCAATAAGGAGTATAG ACTGATCAACTGCAACACCTCTGCCATCACCCAGGCCTGTCCTAAGGTGTCCTTT GAGCCAATCCCAATCCACTATTGCGCCCCTGCCGGCTTTGCCATCCTGAAGTGCA AGGACAAGAAGTTTAACGGCACAGGCCCCTGCCCATCCGTGAGCACAGTGCAGT GTACCCACGGCATCAAGCCTGTGGTGTCCACCCAGCTGCTGCTGAACGGCTCCCT GGCCGAGGAGGAGGTAATCATCAGGTCTGAGAACATCACAAATAACGCCAAGAA CATCCTGGTGCAGCTGAACACCCCAGTGCAGATCAACTGTACCCGGCCTAACAAT AATACCGTGAAGTCTATCCGGATCGGCCCAGGCCAGGCCTTCTACTATACCGGCG ATATCATCGGCGATATCAGACAGGCCCACTGCAACGTGTCCAAGGCCACATGGA ACGAGACACTGGGCAAGGTGGTGAAGCAGCTGCGGAAGCACTTTGGCAATAACA CCATCATCAGATTCGCCCAGTCTTCCGGCGGCGACCTGGAGGTGACAACCCACTC CTTCAATTGCGGCGGCGAGTTCTTTTACTGTAATACAAGCGGCCTGTTTAATAGC ACCTGGATCTCTAACACCTCCGTGCAGGGCTCCAACAGCACAGGCTCTAATGATT CCATCACCCTGCCTTGCCGGATCAAGCAGATCATCAATATGTGGCAGAGAATCGG CCAGGCCATGTATGCCCCTCCAATCCAGGGCGTGATCCGCTGCGTGTCCAACATC ACAGGCCTGATCCTGACAAGAGATGGCGGCTCCACCAACAGCACCACAGAGACC TTCAGACCCGGCGGCGGCGACATGCGCGACAACTGGAGATCCGAGCTGTATAAG TACAAGGTGGTGAAGATCGAGCCCCTGGGCGTGGCCCCAACCCGGTGTAAGCGC AGAGTGGTGGGCAGCCACAGCGGCAGCGGCGGCAGCGGCTCCGGCGGCCACGCC GCCGTGGGCATCGGCGCCGTGTCCCTGGGCTTCCTGGGCGCCGCCGGCTCCACCA TGGGCGCCGCCTCCATGACACTGACAGTGCAGGCCAGAAATCTGCTGTCCGGCAT CGTGCAGCAGCAGTCCAATCTGCTGCGGGCCCCTGAGCCACAGCAGCACCTGCT GAAGGATACCCACTGGGGCATCAAGCAGCTGCAGGCCCGGGTGCTGGCCGTGGA GCACTACCTGAGGGATCAGCAGCTGCTGGGCATCTGGGGCTGTTCCGGCAAGCT GATCTGCTGTACAAACGTGCCCTGGAACAGCTCCTGGTCCAATAGGAACCTGTCC GAGATCTGGGATAACATGACCTGGCTGCAGTGGGATAAGGAGATCAGCAACTAC ACACAGATCATCTACGGCCTGCTGGAGGAGAGCCAGAATCAGCAGGAGAAGAAC GAGCAGGACCTGCTGGCCCTGGATGGAGGAGGAAGCGGGGGAAGCGGGGGAAG CGGAGGAAGCGGGGGAAGCGGGGGAAGCAACGCCGTGGGCCAGGACACCCAGG AAGTGATCGTGGTGCCCCACAGCCTGCCTTTCAAGGTGGTGGTCATCTCCGCCAT CCTGGCCCTGGTCGTGCTGACTATTATTTCCCTGATTATCCTGATTATGCTGTGGC AGAAGAAGCCCAGATGATAA (25) BG505_MD39_TS1_gp140-PDGFR GGATCCGCCACCATGGACTGGACATGGATTCTGTTCCTGGTCGCTGCCGCT ACAAGAGTGCATTCCGCCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCCG TGTGGAAGGACGCCGAGACTACGCTGTTCTGCGCCAGCGATGCCAAGGCCTACG AGACAGAGAAGCACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAA ACCCCCAGGAGATCCACCTGGAGAATGTGACAGAGGAGTTTAACATGTGGAAGA ACAATATGGTGGAGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCT GAAGCCCTGCGTGAAGCTGACCCCTCTGTGCGTGACACTGCAGTGTACCAACGTG ACAAACAATATCACCGACGATATGCGGGGCGAGCTGAAGAATTGTAGCTTCAAC ATGACCACAGAGCTGAGGGACAAGAAGCAGAAGGTGTACTCCCGTGTTTTATAGA CTGGATGTGGTGCAGATCAATGAGAACCAGGGCAATCGGTCTAACAATAGCAAC AAGGAGTACCGCCTGATCAATTGCAACACCTCCGCCATCACACAGGCCTGTCCTA AGGTGTCTTTCGAGCCTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCAT CCTGAAGTGTAAGGATAAGAAGTTTAACGGAACCGGACCATGCCCTTCCGTGTCT ACCGTGCAGTGTACACACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGA ATGGCAGCCTGGCCGAGGAGGAAGTGATCATCAGGTCTGAGAACATCACCAACA ATGCCAAGAATATCCTGGTGCAGCTGAACACACCAGTGCAGATCAATTGCACCC GGCCCAACAATAACACAGTGAAGTCTATCCGCATCGGCCCAGGCCAGGCCTTTTA CTATACCGGCGACATCATCGGCGATATCAGACAGGCCCACTGTAATGTGAGCAA GGCCACCTGGAACGAGACACTGGGCAAGGTGGTGAAGCAGCTGAGGAAGCACTT CGGCAATAACACCATCATCAGATTTGCACAGAGCTCCGGCGGCGACCTGGAGGT GACCACACACTCCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACACAAGCGGC CTGTTTAATTCCACCTGGATCTCCAACACATCTGTGCAGGGCAGCAATTCCACCG GCAGCAACGATTCCATCACACTGCCATGCCGGATCAAGCAGATCATCAACATGT GGCAGCGCATCGGCCAGGCCATGTATGCCCCTCCCATCCAGGGCGTGATCAGAT GCGTGAGCAATATCACCGGCCTGATCCTGACACGCGACGGCGGCTCTACCAACA GCACCACAGAGACATTCCGGCCCGGCGGCGGCGACATGAGGGATAACTGGAGAT CTGAGCTGTACAAGTATAAGGTGGTGAAGATCGAGCCTCTGGGAGTGGCACCAA CCAGGTGCAAGAGGAGAGTGGTGGGCTCTCCAGCGGCTCCGGCGGCTCTGGCA GCGGCGGCCACGCCGCAGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAG CAGCAGGCTCCACAATGGGAGCAGCCTCTATGACCCTGACAGTGCAGGCCAGGA ATCTGCTGAGCGGCATCGTGCAGCAGCAGTCCAACCTGCTGAGAGCCCCAGAGC CCCAGCAGCACCTGCTGAAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCA GGGTGCTGGCAGTGGAGCACTATCTGAGAGATCAGCAGCTGCTGGGCATCTGGG GCTGTAGCGGCAAGCTGATCTGCTGTACCAATGTGCCCTGGAACTCTAGCTGGTC TAATCGCAACCTGAGCGAGATCTGGGACAATATGACCTGGCTGCAGTGGGATAA GGAGATCTCCAACTACACACAGATCATCTATGGCCTGCTGGAAGAATCTCAGAAT CAGCAGGAAAAGAATGAACAGGATCTGCTGGCACTGGATGGCGGCGCCGAAAA CCTGTGGGTCACCGTGTACTACGGAGTCCCCGTGTGGAAAGATGCAGAGACAAC CCTGTTCTGCGCTTCCGACGCTAAAGCTTACGAGACAGAAAAACACAACGTGTG GGCCACTCATGCCTGCGTGCCTACAGACCCTAACCCACAGGAAATCCACCTGGA GAATGTGACGGAGGAGTTTAACATGTGGAAGAATAACATGGTCGAGCAGATGCA TGAAGATATCATTTCCTTATGGGACCAATCCCTGAAGCCTTGCGTGAAGCTGACC CCACTGTGCGTGACACTGCAATGCACTAACGTGACCAATAACATTACCGACGATA TGCGCGGCGAGCTGAAGAACTGCTCTTTCAACATGACTACCGAGCTGAGGATA AGAAACAGAAAGTGTACAGCCTGTTTTATCGGTTAGATGTGGTGCAGATCAATG AAAACCAGGGCAATCGGTCCAACAATTCTAACAAGGAATATCGCCTGATCAATT GTAACACCTCCGCCATTACCCAGGCTTGCCCTAAGGTGTCTTTCGAGCCCATCCC TATCCACTATTGCGCCCCAGCTGGATTTGCTATCCTGAAGTGTAAGGACAAAAAG TTTAACGGGACCGGACCATGTCCTAGCGTGTCCACTGTGCAGTGCACCCATGGCA TCAAGCCTGTGGTGTCCACCCAACTTCTGCTGAATGGCTCTCTGGCTGAAGAAGA AGTGATCATTAGGTCCGAAAATATTACTAATAACGCTAAAAATATCCTGGTCCAG CTGAACACGCCTGTCCAGATCAATTGTACCCGGCCAAATAACACACAGTGAAG TCTATCAGAATCGGCCCAGGCCAGGCCTTCTACTACACAGGCGACATTATCGGCG ATATTCGCCAGGCCCACTGTAATGTGAGCAAAGCTACATGGAATGAGACACTGG GCAAGGTAGTCAAACAGCTGAGAAAACATTTTGGAAACAACACCATCATCCGCT TTGCACAGTCTAGCGGCGGCGACCTGGAGGTAACTACCCACAGCTTCAATTGTGG CGGCGAGTTCTTTTACTGTAATACCAGCGGCCTGTTTAATAGTACTTGGATCAGC AACACATCTGTGCAGGGCTCTAACTCCACTGGTCTAACGATAGCATCACACTGC CTTGTCGGATCAAGCAAATCATCAACATGTGGCAAAGGATTGGGCAGGCTATGT ATGCCCCTCCAATCCAGGGCGTGATCCGGTGCGTGAGCAACATTACAGGCCTGAT CCTGACAAGAGACGGCGGCTCCACCAACTCTACTACCGAGACATTCCGGCCCGG CGGCGGCGACATGCGTGATAATGGCGCAGCGAACTGTATAAATATAAAGTGGT GAAGATCGAGCCTCTGGGCGTGGCCCCAACTAGGTGTAAAAGAAGGGTCGTCGG CTCCCACAGCGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCGGCTGTCGGCAT CGGCGCCGTGAGCCTGGGTTTCTGGGCGCCGCCGGCTCCACTATGGGCGCAGCC TCTATGACCCTGACTGTCCAGGCTAGAAATCTGCTGTCTGGAATCGTGCAGCAGC AGTCTAACCTGCTGAGGGCACCTGAGCCACAACAGCCCTGCTGAAGGATACAC ATGGGGCATCAAGCAGTTACAAGCCAGGGTGCTGGCCGTGGAACACTACCTGC GCGATCAGCAATTACTGGGCATTTGGGGATGCTCTGGCAAGCTGATTTGTTGCAC CAATGTGCCCTGGAACTCCTCTTGGAGCAACAGAAACCTGTCCGAAATCTGGGAT AACATGACATGGCTGCAGTGGGACAAGGAAATTTCCAATTATACCCAGATCATCT ATGGACTGCTGGAAGAAAGTCAGAATCAGCAGGAGAAGAATGAACAGGATCTG CTGGCACTGGATGGCGGCGCCGAAAACCTGTGGGTCACCGTGTATTATGGAGTG CCAGTGTGGAAGGACGCCGAGACCACACTGTTTTGTGCCTCTGATGCCAAGGCCT ACGAGACCGAGAAGCACAACGTGTGGGCCACCCACGCCTGCGTGCCCACAGACC CAAATCCTCAGGAGATCCACCTGGAGAACGTGACCGAGGAGTTTAACATGTGGA AGAACAATATGGTGGAGCAGATGCACCGAGGATATCATCTCTCTGTGGGATCAGT CTCTGAAGCCATGTGTGAAGCTGACCCCACTGTGCGTGACCCTGCAGTGTACAAA TGTGACAAACAACATCACAGATGACATGAGAGGCGAGCTGAAGAACTGTTCCTT CAATATGACCACCGAGCTGAGAGACAAGAAGCAGAAGGTGTATTCTCTGTTTTA CCGGCTGGACGTGGTGCAGATCAACGAGAATCAGGGCAATCGGTCTAACAACTC CAATAAGGAGTATAGACTGATCAACTGCAACACCTCTGCCATCACCCAGGCCTGT CCTAAGGTGTCCTTTGAGCCAATCCCAATCCACTATTGCGCCCCTGCCGGCTTTGC CATCCTGAAGTGCAAGGACAAGAAGTTTAACGGCACAGGCCCCTGCCCATCCGT GAGCACAGTGCAGTGTACCCACGGCATCAAGCCTGTGGTGTCCACCCAGCTGCTG CTGAACGGCTCCCTGGCCGAGGAGGAGGTAATCATCAGGTCTGAGAACATCACA AATAACGCCAAGAACATCCTGGTGCAGCTGAACACCCCAGTGCAGATCAACTGT ACCCGGCCTAACAATAATACCGTGAAGTCTATCCGGATCGGCCCAGGCCAGGCC TTCTACTATACCGGCGATATCATCGGCGATATCAGACAGGCCCACTGCAACGTGT CCAAGGCCACATGGAACGAGACACTGGGCAAGGTGGTGAAGCAGCTGCGGAAG CACTTTGGCAATAACACCATCATCAGATTCGCCCAGTCTTCCGGCGGCGACCTGG AGGTGACAACCCACTCCTTCAATTGCGGCGGCGAGTTCTTTTACTGTAATACAAG CGGCCTGTTTAATAGCACCTGGATCTCTAACACCTCCGTGCAGGGCTCCAACAGC ACAGGCTCTAATGATTCCATCACCCTGCCTTGCCGGATCAAGCAGATCATCAATA TGTGGCAGAGATCGGCCAGGCCATGTATGCCCCTCCAATCCAGGGCGTGATCC GCTGCGTGTCCAACATCACAGGCCTGATCCTGACAAGAGATGGCGGCTCCACCA ACAGCACCACAGAGACCTTCAGACCCGGCGGCGGCGACATGCGCGACAACTGGA GATCCGAGCTGTATAAGTACAAGGTGGTGAAGATCGAGCCCCTGGGCGTGGCCC CAACCCGGTGTAAGCGCAGAGTGGTGGGCAGCCACAGCGGCAGCGGCGGCAGC GGCTCCGGCGGCCACGCCGCCGTGGGCATCGGCGCCGTGTCCCTGGGCTTCCTGG GCGCCGCCGGCTCCACCATGGGCGCCGCCTCCATGACACTGACAGTGCAGGCCA GAAATCTGCTGTCCGGCATCGTGCAGCAGCAGTCCAATCTGCTGCGGGCCCCTGA GCCACAGCAGCACCTGCTGAAGGATACCCACTGGGGCATCAAGCAGCTGCAGGC CCGGGTGCTGGCCGTGGAGCACTACCTGAGGGATCAGCAGCTGCTGGGCATCTG GGGCTGTTCCGGCAAGCTGATCTGCTGTACAAACGTGCCCTGGAACAGCTCCTGG TCCAATAGGAACCTGTCCGAGATCTGGGATAACATGACCTGGCTGCAGTGGGAT AAGGAGATCAGCAACTACACACAGATCATCTACGGCCTGCTGGAGGAGAGCCAG AATCAGCAGGAGAAGAACGAGCAGGACCTGCTGGCCCTGGATGGAGGAGGAAG CGGGGGAAGCGGGGGAAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAACGCC GTGGGCCAGGACACCCAGGAAGTGATCGTGGTGCCCCACAGCCTGCCTTTCAAG GTGGTGGTCATCTCCGCCATCCTGGCCCTGGTCGTGCTGACTATTATTTCCCTGAT TATCCTGATTATGCTGTGGCAGAAGAAGCCCAGA TRO11_AY835545_MD39_L14G8-nucleic acid ATGGATTGGACTTGGATTCTGTTTCTGGTCGCTGCTGCTACTCGGGTGCATTCTCA GGGCCAGCTGTGGGTCACTGTCTACTACGGCGTGCCAGTGTGGAAGGACGCCTCT ACCACACTGTTTTGCGCCAGCGACGCCAAGGCCTACGATACAGAGGTGCACAAC GTGTGGGCAACACACGCATGCGTGCCAACCGATCCAAATCCCCAGGAGGTGGTG CTGGGCAACGTGACCGAGAACTTCAATATGTGGAAGAACAATATGGTGGACCAG ATGCACGAGGATATCATCTCTCTGTGGGACCAGAGCCTGAAGCCCTGCGTGAAG CTGACCCCTCTGTGCGTGACACTGAATTGTACCGATAACATCACCAACACAAATA CCAACAGCTCCAAGAACTCTAGCACACACTCCTATAACAATTCTCTGGAGGGCGA GATGAAGAATTGTTCCTTTAACATCACCGCCGGCATCCGGGACAAGGTGAAGAA GGAGTACGCCCTGTTCTATAAGCTGGATGTGGTGCCCATCGAGGAGGACAAGGA TACAAATAAGACCACATACCGGCTGCGCAGCTGCAACACATCCGTGATCACCCA GGCCTGTCCTAAGGTGACCTTTGAGCCTATCCCAATCCACTATTGCGCCCCAGCC GGCTTCGCCATCCTGAAGTGTAATGACAAGAAGTTTAACGGCACAGGCCCCTGC ACCAACGTGTCTACAGTGCAGTGTACCCACGGCATCAGGCCTGTGGTGTCCACCC AGCTGCTGCTGAATGGCTCTCTGGCCGAGGAGGAAGTGATCATCAGAAGCGAGA ACTTTACAAACAATGCCAAGACCATCATCGTGCAGCTGAATGAGTCTATCGCCAT CAACTGCACAAGGCCAAACAATAACACCGTGAGAAGCATCCACATCGGACCAGG AAGGGCCTTCTACTATACCGGCGACATCATCGGCGATATCAGGCAGGCCCACTGT AATATCTCCAGAACAGAGTGGAACTCTACCCTGCGGCAGATCGTGACAAAGCTG CGCGAGCAGCTGGGCGACCCTAACAAGACCATCATCTTCGCCCAGTCCTCTGGCG GCGATACAGAGATCACCATGCACTCCTTTAATTGCGGCGGCGAGTTCTTTTACTG TAACACCACAAAGCTGTTCAATTCTACCTGGAACGGCAATAACACCACAGAGTC CGACTCTACAGGCGAGAATATCACCCTGCCATGCCGGATCAAGCAGATCATCAA CCTGGTGGCAGGAAGTGGGCAAGGCCATGTATGCCCCTCCCATCAAGGGCCAGAT CTCCTGTAGCTCCAACATCACAGGCCTGCTGCTGACCCGCGACGGCGGAAATAAC AATTCTAGCGGACCAGAGACATTCAGGCCTGGCGGCGGCAATATGAAGGATAAC TGGAGAAGCGAGCTGTACAAGTATAAAGTGATCAAGATCGAGCCTCTGGGAGTG GCACCAACCAGGTGCAAGAGGAGAGTGGTGGGCAGCCACTCCGGCTCTGGCGGC AGCGGCTCCGGCGGCCACGCAGCAGTGGGCACACTGGGCGCCATGAGCCTGGGC TTCCTGGGAGCAGCAGGCAGCACCATGGGAGCAGCATCCGTGACACTGACCGTG CAGGCAAGGCTGCTGCTGTCCGGCATCGTGCAGCAGCAGAACAATCTGCTGAGG GCACCAGAGCCTCAGCAGCACATGCTGCAGGACACACACTGGGGCATCAAGCAG CTGCAGGCCCGGGTGCTGGCAGTGGAGCACTACCTGCGCGATCAGCAGCTGCTG GGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACCAATGTGCCTTGGAACG CCTCTTGGAGCAATAAGAGCCTGAACAATATCTGGGAGAATATGACATGGATGA ACTGGTCCAGAGAGATCGACAACTACACCGATCTGATCTATATCCTGCTGGAGAA GTCACAGATTCAGCAGGAGAAGAACAATCAGAGCCTGCTGGAACTGGAT X2278_FJ817366_MD39_L14G8-nucleic acid ATGGACTGGACCTGGATTCTGTTCCTGGTCGCCGCTGCTACAAGAGTGCAT TCTACAAATAACCTGTGGGTGACTGTCTACTATGGAGTGCCCGTGTGGAAGGAGG CCACCACAACCCTGTTCTGCGCCAGCGAGGCCAAGGCCTACGACACAGAGGTGC ACAACATCTGGGCCACCCACGCCTGCGTGCCTACAGATCCAAACCCCCAGGAGA TGGAGCTGAAGAATGTGACCGAGAACTTCAACATGTGGAAGAACAATATGGTGG AGCAGATGCACGAGGACATCATCAGCCTGTGGGATCAGTCCCTGAAGCCCTGCG TGAAGCTGACACCTCTGTGCGTGACCCTGGATTGTACAAATATCAACAGCACAAA CTCCACCAACAATACAAGCTCCAATTCTAAGATGGAGGAGACAATCGGCGTGAT CAAGAATTGTAGCTTCAACGTGACAACCAATATCCGGGACAAGGTGAAGAAGGA GAACGCCCTGTTTTACTCTCTGGATCTGGTGAGCATCGGCAATTCTAACACCAGC TATCGCCTGATCTCCTGCAATACCTCTATCATCACACAGGCCTGTCCAAAGGTGA GCTTCGACCCTATCCCAATCCACTACTGCGCACCAGCAGGATTCGCAATCCTGAA GTGTAGGGATAAGAAGTTTAACGGCACCGGCCCTTGCAGAAACGTGAGCAGCGT GCAGTGTACACACGGCATCAGGCCAGTGGTGAGCACCCAGCTGCTGCTGAACGG CTCCCTGGCAGAGGAGGAGATCATCATCAGATCCGCCAACCTGACCGACAATGC CAAGACAATCATCATCCAGCTGAACGAGACAATCCAGATCAATTGCACAAGGCC CAACAATAACACCGTGAGAAGCATCCCAATCGGCCCCGGCCGGACCTTTTACTAT ACAGGCGACATCATCGGCGATATCCGCAAGGCCTACTGTAACATCTCCGCCACCA AGTGGAATAACACACTGCGGCAGATCGCCGAGAAGCTGCGCGAGAAGTTCAACA AGACAATCATCTTTGCCCAGTCCTCTGGCGGCGATCCAGAGGTGGTGAGGCACAC CTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACAGCTCCCAGCTGTTTAATAGC ACATGGTATTCCAACGGCACCTCTAATGGCGGCCTGAATAACAGCGCCAACATC ACCCTGCCCTGCAGAATCAAGCAGATCATCAATCTGTGGCAGGAAGTGGGCAAG GCCATGTATGCCCCTCCCATCAAGGGCGTGATCAACTGTCTGTCCAATATCACCG GCATCATCCTGACAAGGGACGGCGGCGAGAATAACGGCACAACCGAGACATTCA GACCCGGCGGCGGCGACATGAGGGATAACTGGCGCTCTGAGCTGTACAAGTATA AGGTGGTGAAGATCGAGCCTCTGGGCATCGCCCCAACCAAGTGCAAGAGGAGAG TGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGCCACGCAGCAG TGGGCCTGGGAGCCGTGTCTCTGGGCTTTCTGGGCCTGGCAGGCTCCACAATGGG AGCAGCCTCTGTGACACTGACCGTGCAGGCAAGGCTGCTGCTGAGCGGCATCGT GCAGCAGCAGAATAACCTGCTGAGGGCACCAGAGCCTGCAGCAGCAGCTGCTGCA GGACACCCACTGGGGCATCAAGCAGCTGCAGGCCCGGGTGCTGGCCCTGGAGCA CTACCTGAAGGATCAGCAGCTGCTGGGCATCTGGGGCTGTTCCGGCAAGCTGATC TGCTGTACAACCGTGCCATGGAACGCCTCCTGGTCTAACAAGTCCTATAATCAGA TCTGGAATAACATGACATGGATGAACTGGAGCAGGGAGATCGACAATTACACCA ACCTGATCTATAATCTGATTGAAGAGTCACAGTCACAGCAGGAAAAGAACAACC TGAGCCTGCTGCAGCTGGAC 398F1_HM215312_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTTCTGGTCGCAGCCGCAACTAGAGTGCAT AGCATGGGCAACCTGTGGGTCACCGTGTATTACGGGGTGCCAGTGTGGAAGGAC GCCGAGACTACGCTGTTCTGCGCCTCCGATGCCAAGGCCTACCACACAGAGGTGC ACAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCAAATCCCCAGGAGA TCAACCTGGAGAATGTGACCGAGGAGTTTAACATGTGGAAGAATAAGATGGTGG AGCAGATGCACGAGGACATCATCTCCCTGTGGGATCAGTCTCTGAAGCCTTGCGT GCAGCTGACCCCACTGTGCGTGACACTGGACTGTCAGTACAACGTGACCAACATC AATAGCACATCCGATATGGCCAGGGAGATCAACAATTGTAGCTATAATATCACC ACAGAGCTGCGGGATCGCGAGCAGAAAGTGTACAGCCTGTTCTATAGGTCCGAC ATCGTGCAGATGAACTCCGATAATAGCTCCAAGTACAGACTGATCAACTGCAAT ACCTCTGCCATCAAGCAGGCCTGTCCAAAGGTGACATTTGAGCCTATCCCAATCC ACTATTGCGCACCAGCAGGATTCGCAATCCTGAAGTGTAAGGACAAGGAGTTTA ACGGCACCGGCCCTTGCAAGAACGTGAGCACCGTGCAGTGTACACACGGCATCA AGCCAGTGGTGAGCACACAGCTGCTGCTGAACGGCTCCCTGGCCGAGGAGAAAG TGATCATCCGGTCTGAGAATATCACCGATAACGCCAAGAATATCATCGTGCAGCT GAAGGAGCCCGTGAAGATCAACTGCACCCGGCCTAACAATAACACAGTGAAGTC CGTGCGCATCGGCCCTGGCCAGACCTTCTACTATACAGGCGAGATCATCGGCGAC ATCCGCCAGGCCCACTGTAACGTGTCTAAGGCCCACTGGGAGAACACCCTGCAG GAGGTGGCCAATCAGCTGAAGCTGATGATCCACAGCAACAAGACAATCATCTTC GCCAATTCTAGCGGCGGCGATCTGGAGATCACCACACACTCTTTTAACTGCGGCG GCGAGTTCTTTTACTGTTATACCAGCGGCCTGTTCAACTACACCTTCAACGACAC CAGCACAAACTCCACCGAGTCTAAGAGCAATGATACCATCACACTGCAGTGCAG GATCAAGCAGATCATCAACATGTGGCAGAGAGCAGGACAGGCCGTGTATGCCCC TCCCATCCCCGGCATCATCCGGTGTGAGAGCAATATCACCGGCCTGATCCTGACA CGCGACGGCGGAAATAACAATTCCAACACCAATGAGACATTCAGGCCCGGCGGC GGCGACATGAGGGATAACTGGAGATCTGAGCTGTACAGATATAAGGTGGTGAAG ATCGAGCCAATCGGCGTGGCCCCCACCACATGCAAGAGGAGAGTGGTGGGCTCC CACTCTGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCCGTGGGCATCGGA GCCGTGAGCCTGGGCTTTCTGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAGC ATCACCCTGACAGTGCAGGCAAGGCAGCTGCTGTCCGGAATCGTGCAGCAGCAG TCTAACCTGCTGAGGGCACCAGAGCCTCAGCAGCACCTGCTGAAGGACACCCAC TGGGGCATCAAGCAGCTGAAGGCCAGGGTGCTGGCCGTGGAGCACTACCTGAAG GATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACCA ACGTGCCCTGGAATTCCTCTTGGTCTAACAAGAGCCTGGGCGAGATCTGGGACAA CATGACCTGGCTGAATTGGTCCAAGGAGATCGAGAATTACACACAGATCATCTAT GAGCTGATTGAAGAGTCACAGAACCAGCAGGAGAAAAACAACCAGAGCCTGCT GGCACTGGAT 246F3_HM215279_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTTCTGGTCGCAGCCGCTACTCGGGTGAC TCTATGCAGGACCTGTGGGTGACCGTCTATTATGGGGTGCCAGTGTGGAAGGACG CCAAGACCACACTGTTCTGCGCCTCCGATGCCAAGGCCTACGAGAAGGAGGTGC ACAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCAAACCCCCAGGAGA TCGTGATGGCCAATGTGACCGAGGAGTTTAACATGTGGAAGAACAATATGGTGG AGCAGATGCACGAGGACATCATCTCTCTGTGGGATCAGAGCCTGAAGCCTTGCGT GAAGCTGACCCCACTGTGCGTGACACTGGACTGTAAGGATTACAACTATTCCATC ACCAACAATTCTACAGGCATGGAGGGCGAGATCAAGAATTGTTCTTATAACATC ACCACAGAGCTGCGCGACAAGAGGCAGAAAGTGTACAGCCTGTTCTATCGCCTG GATGTGGTGCAGATCAATGACTCTAACGATCGCAACAATAGCCAGTACAGGCTG ATCAATTGCAACACCACAACCATGACCCAGGCCTGTCCTAAGGTGACATTTGACC CTATCCCAATCCACTATTGCGCCCCAGCCGGCTTCGCCATCCTGAAGTGTAACAA TAAGACCTTTAATGGCAAGGGCCCCTGCAACAATGTGAGCTCCGTGCAGTGTACC CACGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAACGGCAGCCTGGCCG AGAAGGAGATCATCATCAGGAGCGAGAATCTGACCGACAACGTGAAGACAATCA TCGTGCACCTGAATGAGAGCGTGGAGATCAACTGCACCAGACCAAACAATAACA CAGTGAAGTCCGTGCGGATCGGACCAGGACAGACCTTCTACTATACAGGCGATA TCATCGGCAATATCCGCCAGGCCCACTGTACCGTGAATAAGACAGAGTGGAACA CAGCCCTGACCAGGGTGAGCAAGAAGCTGAAGGAGTACTTCCCCAACAAGACCA TCGCCTTTCAGCCTTCTAGCGGCGGCGACCTGGAGATCACAACCTTCTCCTTTAAT TGCAGAGGCGAGTTCTTTTATTGTAACACATCCGATCTGTTCAATGGCACCTTTA ACGAGACATCTGGCCAGTTCAATTCCACCTTTAACTCTACACTGCAGTGCCGGAT CAAGCAGATCATCAATATGTGGCAGGAAGTGGGACAGGCAATGTACGCCCCTCC CATCGCAGGCAGCATCACCTGTATCTCCAACATCACCGGCCTGATCCTGACACGC GACGGCGGAAATACAAACTCCACCAAGGAGACATTCAGGCCTGGCGGCGGCAAT ATGAGAGATAACTGGCGGTCTGAGCTGTACAAGTATAAGGTGGTGAAGATCGAG CCACTGGGAGTGGCACCAACCAAGTGCAGGAGACGGGTGGTGGGCAGCCACTCC GGCTCTGGCGGCAGCGGCTCCGGCGGCCACGCAGCAGTGGGCATCGGCGCCGTG TCTATCGGCTTTCTGGGAGCAGCAGGCTCCACCATGGGAGCAGCCTCTATCACAC TGACCGTGCAGGCCAGACAGCTGCTGAGCGGCATCGTGCAGCAGCAGTCCAACC TGCTGAGGGCACCAGAGCCTCAGCAGCACCTGCTGAAGGACACCCACTGGGGCA TCAAGCAGCTGCAGGCCAGGGTGCTGGCAGTGGAGCACTACCTGAAGGATCAGC AGCTGCTGGGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACAAATGTGCC CTGGAACTCCTCTTGGTCTAACAAGAGCCAGGACGAGATCTGGGATAATATGAC CTGGCTGAACTGGAGCAAGGAGATCTCCAATTACACACAGATCATCTATAACCTG ATTGAAGAATCACAGACTCAGCAGGAACTGAATAATAGGTCACTGCTGGCACTG GAT CE0217_FJ443575_MD39_L14G8 ATGGACTGGACTTGGATTCTGTTTCTGGTCGCCGCCGCAACTCGCGTGCAT TCAGCAAAAGATATGTGGGTCACCGTCTATTATGGAGTGCCCGTGTGGCGGGAG GCCAAGACCACACTGTTTTGCGCAAGCGACGCAAAGGCATACGAGAGGGAGGTG CACAACGTGTGGGCCACACACGCCTGCGTGCCAACCGATCCAAATCCCCAGGAG AGAGTGCTGGAGAACGTGACCGAGAATTTCAACATGTGGAAGAACAATATGGTG GACCAGATGCACGAGGATATCATCTCTCTGTGGGACGAGAGCCTGAAGCCCTGC ATCAAGCTGACACCTCTGTGCGTGACCCTGAATTGTGGCAACGCCATCGTGAATG AGTCCACCATCGAGGGCATGAAGAATTGTTCTTTTAACGTGACCACAGAGCTGAA GGACAAGAAGAAGAAGGAGTACGCCCTGTTCTATAAGCTGGATGTGGTGCCCCT GAACGGCGAGAACAACAACTCTAACAGCAAGAACTTTAGCGAGTACAGGCTGAT CAATTGCAACACCTCCACAATCACCCAGGCCTGTCCCAAGGTGTCTTTCGATCCT ATCCCAATCCACTATTGCGCCCCTGCCGGCTTCGCCATCCTGAAGTGTAATAACG AGACATTCAACGGCACCGGCCCATGCAATAACGTGTCCACAGTGCAGTGTACCC ACGGCATCAAGCCCGTGGTGTCTACACAGCTGCTGCTGAATGGCAGCCTGGCCG AGAAGGAGATCATCATCAGGTCTGAGAACCTGACCAATAACGCCAAGATCATCA TCGTGCACCTGAATAACCCAGTGAAGATCATCTGCACAAGGCCCGGCAATAACA CCGTGAAGAGCATGAGAATCGGCCCTGGCCAGACATTCTACTATACCGGCGACA TCATCGGCGATATCAGGAGAGCCTACTGTAACATCTCTGAGAAGACATGGTATG ACACCCTGAAGAATGTGAGCGATAAGTTCCAGGAGCACTTTCCTAACGCCTCCAT CGAGTTCAAGCCATCTGCCGGCGGCGACCTGGAGATCACCACACACTCCTTTAAT TGCAGGGGCGAGTTCTTTTACTGTGATACAAGCGAGCTGTTCAATGGCACATACA ATAACTCCACCTATAACAGCTCCAATAACATCACCCTGCAGTGCAAGATCAAGCA GATCATCAACATGTGGCAGGGCGTGGGCAGAGCCATGTATGCCCCTCCCATCGCC GGCAATATCACCTGTGAGAGCAACATCACAGGCCTGCTGCTGACCCGGGACGGC GGAAATAACAAGTCCACACCAGAGACATTCAGGCCCGGCGGCGGCGACATGAGG GATAACTGGAGAAGCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGCCTCTG GGCATCGCCCCAACAAAGTGCAAGAGGAGGGTGGTGGGCTCCCACTCTGGCAGC GGCGGCTCCGGCTCTGGCGGCCACGCAGCCGTGGGCATGGGCGCCGTGTCTCTG GGCTTCCTGGGAGCAGCAGGCAGCACCATGGGAGCAGCATCCCTGACACTGACC GTGCAGGCAAGGCAGCTGCTGAGCGGCATCGTGCAGCAGCAGAATAACCTGCTG AGAGCCCCCGAGCCTCAGCAGCACATGCTGCAGGACACACACTGGGGCATCAAG CAGCTGCAGGCCCGGGTGCTGGCAATCGAGCACTACCTGACAGATCAGCAGCTG CTGGGCATCTGGGGCTGTTCCGGCAAGCTGATCTGCTGTACCAATGTGCCCTGGA ATAACAGCTGGTCCAACAAGTCCTATGAGGATATCTGGGGCCGGAATATGACCT GGATGAACTGGAGCAGGGAGATCAACAACTACACAAACACCATCTATCGCCTGC TGGAAAAGTCACAGAATCAGCAGGAGAAGAATAATAAGTCACTGCTGGAACTGG AC CE1176_FJ444437_MD39_L1468-nucleic acid ATGGATTGGACTTGGATTCTGTTTCTGGTCGCCGCCGCTACTCGCGTGCAT TCAGTGGGCAACCTGTGGGTCACCGTCTACTATGGGGTGCCCGTGTGGAAGGAG GCCAAGACCACACTGTTCTGCGCCTCCGACGCCAAGGCCTACGAGAAGGAGGTG CACAACGTGTGGGCCACACACGCCTGCGTGCCTACCGATCCAAATCCCCAGGAG ATGGTGCTGGAGAACGTGACAGAGAACTTTAATATGTGGAAGAACGACATGGTG GATCAGATGCACGAGGACGTGATCTCTCTGTGGGATCAGAGCCTGAAGCCTTGC GTGAAGCTGACCCCACTGTGCGTGACCCTGACATGTACCAATACCACAGTGTCCA ACGGCAGCTCCAACTCTAATGCCAACTTCGAGGAGATGAAGAATTGTTCTTTTAA CGCCACCACAGAGATCAAGGACAAGAAGAAGAACGAGTACGCCCTGTTCTATAA GCTGGATATCGTGCCCCTGAACAATTCTAGCGGCAAGTATAGGCTGATCAATTGC AACACAAGCGCCATCGCCCAGGCCTGTCCAAAGGTGACCTTCGAGCCTATCCCA ATCCACTACTGCGCCCCCGCCGGCTATGCCATCCTGAAGTGTAACAACAAGACCT TCAACGGCACCGGCCCTTGCAACAACGTGAGCACAGTGCAGTGTACCCACGGCA TCAAGCCAGTGGTGAGCACCCAGCTGCTGCTGAACGGCTCCCTGGCAGAGAAGG AGATCATCATCCGGAGCGAGAATCTGACAAACAATGCCAAGACCATCATCATCC ACCTGAACGAGTCCGTGGGCATCGTGTGCACACGGCCCAGCAACAATACCGTGA AGTCCATCCGCATCGGCCCTGGCCAGACCTTCTACTATACCGGCGACATCATCGG CGATATCCGCCAGGCCCACTGTAATGTGAGCAAGCAGAATTGGAACAGGACACT GCAGCAAGTGGGCAGAAAGCTGGCCGAGCACTTCCCAAATAGGAACATCACCTT TGCCCACTCCTCTGGCGGCGACCTGGAGATCACCACACACTCCTTCAACTGCAGA GGCGAGTTCTTTTACTGTAATACATCTGGCCTGTTTAACGGCACCTACCACCCCA ATGGCACATATAACGAGACAGCCGTGAATAGCTCCGATACAATCACCCTGCAGT GCAGGATCAAGCAGATCATCAACATGTGGCAGGAAGTGGGCAGAGCCATGTATG CCCCTCCCATCGCCGGCAATATCACCTGTAACAGCACAATCACCGGCCTGCTGCT GACACGGGACGGCGGCATCAACCAGACCGGAGAGGAGATCTTCCGCCCCGGCGG CGGCGACATGCGGGATAATTGGCGCAACGAGCTGTACAAGTATAAGGTGGTGGA GATCAAGCCACTGGGCATCGCCCCCACAAAGTGCAAGAGGAGAGTGGTGGCTC CCACTCTGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCCGTGGGCATCGG AGCCGTGTCCCTGGGTTTCTGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAG CATCACACTGACCGTGCAGGCAAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCA GTCTAACCTGCTGAGAGCCCCCGAGCCTCAGCAGCACATGCTGCAGGACACCCA CTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCCATCGAGCACTACCTGAA GGATCAGCAGCTGCTGGGCATCTGGGGCTGTTCTGGCAAGCTGATCTGCTGTACA AATGTGCCATGGAACTCTAGCTGGAGCAACCGGTCCCAGGAGGACATCTGGAAC AATATGACCTGGATGAATTGGAGCAGGGAGATCGATAACTACACACACACCATC TATAGCCTGCTGGAGGAGTCACAGATTCAGCAGGAGAAAAATAATAAGTCACTG CTGGCACTGGAC 25710_EF117271_MD39_L146G8-nucleic acid ATGGACTGGACTTGGATTCTGTTCCTGGTCGCCGCCGCTACTCGCGTGCAT TCTGGGGGCAACCTGTGGGTCACCGTGTATTATGGAGTGCCCGTGTGGAAGGAG GCCACCACAACCCTGTTCTGCGCCAGCGACGCCAAGGCCTACGATAAGGAGGTG CACAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCAAACCCCCAGGAG ATGGTGCTGGGCAATGTGACCGAGAACTTTAATATGTGGAAGAACGAGATGGTG AATCAGATGCACGAGGACGTGATCTCCCTGTGGGATCAGTCTCTGAAGCCTTGCG TGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTTCCAACGTGACCTATAATGA GTCTATGAAGGAGGTGAAGAACTGTTCCTTCAATCTGACAACCGAGCTGAGGGA TAAGAAGCAGAAGGTGCACGCCCTGTTTTACAGACTGGACATCGTGCCCCTGAA CGATACCGAGAAGAAGAATAGCTCCCGGCCTTATCGCCTGATCAACTGCAATAC AAGCGCCATCACCCAGGCCTGTCCTAAGGTGACCTTCGACCCTATCCCAATCCAC TACTGCACACCAGCCGGCTATGCCATCCTGAAGTGTAACGATAAGAAGTTTAATG GCACCGGCCCATGCCACAAGGTGTCCACAGTGCAGTGTACCCACGGCATCAAGC CCGTGGTGTCTACACAGCTGCTGCTGAACGGCAGCCTGGCAGAGGGCGAGATCA TCATCAGGAGCGAGAACCTGACCAACAATGCCAAGACAATCATCGTGCACCTGA ATCAGTCCGTGGAGATCGTGTGCGCCCGGCCAAGCAACAATACAGTGACCTCCA TCAGGATCGGACCAGGACAGACATTCTACTATACCGGCGCCATCACAGGCGACA TCAGGCAGGCCCACTGTAACATCAGCAAGGATAAGTGGAATGAGACACTGCAGA GAGTGGGCGAGAAGCTGGCCGAGCACTTCCCCAACAAGACAATCAAGTTTGCCT CTAGCTCCGGCGGCGACCTGGAGATCACAACCCACTCCTTTAACTGCAGGGGCG AGTTCTTTTACTGTAATACCTCTGGCCTGTTCAACGGCACCTTTAATGGCACATAC GTGAGCCCCAACAGCACCGATTCCAATTCTAGCTCCATCATCACAATCCCTTGCC GGATCAAGCAGATCATCAATATGTGGCAGGAAGTGGGAAGGGCAATGTACGCCC CTCCCATCGCCGGCAACATCACCTGTAAGTCCAATATCACAGGCCTGCTGCTGGT GAGGGACGGCGGAACCGGCTCTGAGAGCAACAAGACAGAGATCTTCAGACCCG GCGGCGGCGACATGAGGGATAATTGGAGATCTGAGCTGTACAAGTATAAGGTGG TGGAGATCAAGCCACTGGGCGTGGCCCCACCAAGTGCAAGAGGAGAGTGGTGG GCTCCCACTCTGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCCGTGGGCAT CGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGCTCTACAATGGGAGCAGC CAGCATCACACTGACCGTGCAGGCAAGGCAGCTGCTGAGCGGCATCGTGCAGCA GCAGTCCAACCTGCTGAGGGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACAC CCACTGGGGCATCAAGCAGCTGCAGACACGGGTGCTGGCCATCGAGCACTACCT GAAGGATCAGCAGCTGCTGGGCATCTGGGGCTGTTCTGGCAAGCTGATCTGCTGT ACCGCCGTGCCCTGGAACTATAGCTGGTCCAATCGCAGCCAGGACGATATCTGG GACAACATGACATGGATGAATTGGTCTAAGGAGATCAGCAACTACACAAATACC ATCTATAAGCTGCTGGAAGATAGTCAGATTCAGCAGGAAAAGAACAATAAGTCA CTGCTGGCACTGGAT BJOX2000_HM215364_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTTCTGGTCGCAGCAGCAACTCGGGTGCAT AGCGTCGGCAACCTGTGGGTCACTGTCTACTACGGGGTGCCCGTGTGGAAGGAG GCCACCACAACCCTGTTCTGCGCCAGCGACGCCAAGGCCTACGATACCGAGGTG CACAACGTGTGGGCAACCCACGCATGCGTGCCTACAGACCCAGATCCCCAGGAG ATGTTCCTGGAGAACGTGACAGAGAACTTCAACATGTGGAAGAACAATATGGTG GACCAGATGCACGAGGATGTGATCAGCCTGTGGGACCAGTCCCTGAAGCCTTGC GTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTAAGAATGTGAACAGCTCC TCTAGCGACACCAAGAACGGCACAGATCCTGAGATGAAGAATTGTTCTTTCAAC GCCACAACCGAGCTGCGGGACCGCAAGCAGAAGGTGTACGCCCTGTTTTATAAG CTGGATATCGTGCCACTGAATGAGAAGAACTCCTCTGAGTATCGGCTGATCAAT GCAACACAAGCACCATCACACAGGCCTGTCCCAAGGTGACCTTCGACCCTATCCC AATCCACTACTGCACACCTGCCGGCTATGCCATCCTGAAGTGTAATGATGAGAAG TTTAACGGCACCGGCCCATGCTCCAACGTGAGCACCGTGCAGTGTACACACGGC ATCAAGCCCGTGGTGAGCACACAGCTGCTGCTGAACGGCTCCCTGGCCGAGAAG GGCATCATCATCCGCTCCGAGAATCTGACCAACAATGTGAAGACAATCATCGTGC ACCTGAACCAGTCCGTGGAGATCCTGTGCATCCGGCCAAACAATAACACCGTGA AGTCTATCCGCATCGGCCCCGGCCAGACCTTCTACTATACAGGCGAGATCATCGG CGACATCCGGCAGGCCCACTGTAATATCTCTGGCAAGGTCTGGAACGAGACACT GCAGAGGGTGGGAGAGAAGCTGGCAGAGTACTTCCCAAACAAGACAATCAAGTT TGCCAGCTCCTCTGGCGGCGATCTGGAGATCACAACCCACTCTTTTAATTGCGGC GGCGAGTTCTTTTACTGTAACACCAGCAAGCTGTTCAATGGCACCTTTAACGGCA CATATATGCCTAATGTGACCGAGGGCAACAGCACAATCTCCATCCCATGCCGGAT CAAGCAGATCATCAATATGTGGCAGAAAGTGGGCCGCGCCATGTATGCCCCTCC CATCGAGGGCAACATCACCTGTAAGAGCAAGATCACAGGCCTGCTGCTGGAGAG GGACGGCGGACCAGAGAACGATACCGAGATCTTCAGACCCGGCGGCGGCGACAT GAGGAATAACTGGAGATCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGCC ACTGGGAGTGGCACCAACCGAGTGCAAGAGGAGAGTGGTGGGCTCTCACAGCGG CTCCGGCGGCTCTGGCAGCGGCGGCCACGCCGCCGTGGGCATCGGAGCCGTGAG CCTGGGCTTTCTGGGAGTGGCAGGCTCTACCATGGGAGCAGCAAGCATGGCACT GACAGTGCAGGCCAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCAGTCTAATCT GCTGAGAGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACACCCACTGGGGCAT CAAGCAGCTGCAGACAAGGGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCA GCTGCTGGGCATCTGGGGCTGTTCCGGCAAGCTGATCTGCTGTACCGCCGTGCCT TGGAATAGCTCCTGGTCTAACAAGAGCCAGGAGGAGATCTGGGAGAATATGACA TGGATGAACTGGTCCAAGGAGATCTCTAACTACACCGATACAATCTATAGACTGC TGGAAGATAGTCAGAATCAGCAGGAGAGAAATAATAAGTCACTGCTGGCACTGG AT CH119_EF117261_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTTCTGGTCGCAGCCGCAACTCGCGTGCAT TCCGTGGGCAACCTGTGGGTCACCGTCTACTATGGGGTGCCAGTGTGGAAGGAG GCCACCACAACCCTGTTCTGCGCCTCCGACGCCAAGGCCTACGATACCGAGGTGC ACAACGTGTGGGCAACACACGCATGCGTGCCAACCGACCCATCTCCCCAGGAGC TGGTGCTGGAGAATGTGACAGAGAACTTCAACATGTGGAAGAATGAGATGGTGA ACCAGATGCACGAGGACGTGATCTCCCTGTGGGATCAGTCTCTGAAGCCTTGCGT GAAGCTGACACCACTGTGCGTGACCCTGGAGTGTTCCAAGGTGTCTAACAATGA GACAGACAAGTATAACGGCACCGAGGAGATGAAGAATTGTAGCTTCAACGCAAC AACCGTGGTGCGGGACCGCCAGCAGAAGGTGTACGCCCTGTTTTATAGGCTGGA TATCGTGCCCCTGACCGAGAAGAATAGCTCCGAGAACTCTAGCAAGTACTATAG ACTGATCAATTGCAACACATCTGCCATCACCCAGGCCTGTCCAAAGGTGAGCTTC GAGCCTATCCCAATCCACTACTGCACCCCCGCCGGCTATGCCATCCTGAAGTGTA ATGACAAGACCTTCAACGGCACCGGCCCTTGCCACAACGTGAGCACAGTGCAGT GTACCCACGGCATCAAGCCAGTGGTGAGCACACAGCTGCTGCTGAATGGCTCCT GGCCGAGGGCGAGATCATCATCCGGTCCGAGAACCTGACAAACAATGTGAAGAC CATCCTGGTGCACCTGAATCAGAGCGTGGAGATCGTGTGCACACGGCCCAACAA TAACACCGTGAAGTCCATCCGCATCGGCCCTGGCCAGACATTCTACTATACCGGC GACATCATCGGCGATATCCGGCAGGCCCACTGTAACATCTCCAAGTGGCACGAG ACACTGAAGCGCGTGTCTGAGAAGCTGGCCGAGCACTTCCCTAATAAGACAATC AACTTTACCTCCTCTAGCGGCGGCGACCTGGAGATCACAACCCACTCTTTCACCT GCCGCGGCGAGTTCTTTTACTGTAATACAAGCGGCCTGTTTAACTCCACATACAT GCCCAATGGCACCTATCTGCACGGCGATACAAATTCCAACTCCTCTATCACCATC CCTTGCAGGATCAAGCAGATCATCAACATGTGGCAGGAAGTGGGCAGAGCCATG TATGCCCCTCCCATCGAGGGCAACATCACCTGTAAGTCTAATATCACAGGCCTGC TGCTGGTGCGGGACGGCGGAACCGAGAGCAATAACACAGAGACAAATAACACA GAGATCTTCCGCCCCGGCGGCGGCGACATGAGGGATAACTGGAGAAGCGAGCTG TACAAGTATAAGGTGGTGGAGATCAAGCCACTGGGAGTGGCACCAACCGCATGC AAGAGGAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGCGGCGGC CACGCCGCCGTGGGCATCGGAGCCGTGTCCCTGGGCTTTCTGGGAGTGGCAGGCT CTACCATGGGAGCAGCCAGCATGACACTGACCGTGCAGGCAAGGCAGCTGCTGT CCGGCATCGTGCAGCAGCAGTCTAACCTGCTGAGAGCACCAGAGCCTCAGCAGC ACCTGCTGCAGGACACCCACTGGGGCATCAAGCAGCTGCAGACACGGGTGCTGG CCATCGAGCACTACCTGAAGGATCAGCAGCTGCTGGGCATCTGGGGCTGTAGCG GCAAGCTGATCTGCTGTACCGCCGTGCCTTGGAATAGCTCCTGGAGCAACAAGTC CCAGAAGGAGATCTGGGATAATATGACATGGATGAACTGGTCTAAGGAGATCAG CAATTACACAAACACCATCTATAAGCTGCTGGAGGACTCACAGAATCAGCAGGA ATCAAACAACAAATCCCTGCTGGCACTGGAC X1632_FJ817370_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTCCTGGTCGCCGCCGCTACACGGGTGCAT TCATCAAATAACCTGTGGGTCACTGTCTACTATGGGGTGCCCGTGTGGGAGGACG CCGATACCACACTGTTCTGCGCATCCGACGCAAAGGCATACTCCACCGAGTCTCA CAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCAAACCCCCAGGAGAT CTATCTGGAGAACGTGACAGAGGACTTCAACATGTGGGAGAACAATATGGTGGA GCAGATGCAGGAGGACATCATCAGCCTGTGGGATGAGTCCCTGAAGCCTTGCGT GAAGCTGACCCCACTGTGCGTGACACTGACCTGTACAAATGTGACCAACGTGAC AGACTCTGTGGGCACAAATAGCCGCCTGAAGGGCTACAAGGAGGAGCTGAAGAA CTGTAGCTTCAATACCACAACCGAGATCAGGGATAAGAAGAAGCAGGAGTACGC CCTGTTTTATAAGCTGGACATCGTGCCAATCAATGATAACAGCAACAATTCCAAC GGCTACAGACTGATCAATTGCAACGTGTCCACCATCAAGCAGGCCTGTCCAAAG GTGTCTTTCGACCCTATCCCAATCCACTATTGCGCACCAGCAGGATTCGCAATCC TGAAGTGTCGCGATAAGGAGTTTAATGGCACCGGCACATGCAGGAACGTGAGCA CCGTGCAGTGTACACACGGCATCAAGCCCGTGGTGTCTACCCAGCTGCTGCTGAA TGGCAGCCTGGCCGAGGGCGACATCATCATCAGATCCGAGAACATCACCGATAA TGCCAAGACAATCATCGTGCACCTGAACAAGACCGTGAGCATCACCTGCACACG CCCCAACAATAACACAGTGAAGTCCATCAGGATCGGCCCTGGCCAGGCCCTGTA CTATACCGGAGCAATCATCGGCGACACAAGGCAGGCCCACTGTAATATCAACGG CTCCGAGTGGTACGAGATGATCCAGAATGTGAAGAACAAGCTGAATGAGACATT CAAGAAGAACATCACATTTGCCCCAGCTCCGGCGGCGATCTGGAGATCACAAC CCACTCTTTTAACTGCCGCGGCGAGTTCTTTTATTGTAACACCAGCGAGCTGTTCA ATTCTAGCCACCTGTTTAACGGCTCTACCCTGAGCACAAACGGCACCATCACACT GCCTTGCAGGATCAAGCAGATCGTGCGCATGTGGCAGAGGGTGGGACAGGCAAT GTACGCCCCTCCCATCGCCGGCAATATCACCTGTAGATCTAACATCACCGGCCTG CTGCTGACACGGGACGGCGGAACCAACAAGGATACAAATGAGGCAGAGACATTC AGACCCGGCGGCGGCGACATGAGAGATAACTGGCGGAGCGAGCTGTACAAGTAT AAGGTGGTGAAGATCAAGCCACTGGGAGTGGCACCAACCAGGTGCAGGAGACG GGTGGTGGGCAGCCACTCCGGCTCTGGCGGCAGCGGCTCCGGCGGCCACGCAGC AATCGGCCTGGGCACCGTGAGCCTGGGCTTTCTGGGAACCGCAGGCTCCACAAT GGGAGCAGCCTCTATCACCCTGACAGTGCAGGTGAGACAGCTGCTGAGCGGCAT CGTGCAGCAGCAGTCCAACCTGCTGAGGGCACCAGAGCCTCAGCAGCACCTGCT GCAGGACACCCACTGGGGCATCAAGCAGCTGCAGGCCCGCGTGCTGGCAGTGGA GCACTACCTGAAGGATCAGCAGATCCTGGGCATCTGGGGCTGTTCCGGCAAGCT GATCTGCTGTACCAACGTGCCCTGGAATTCCTCTTGGTCTAATAAGTCTTATAGC GACATCTGGGATAACCTGACATGGATCAATTGGTCCAGGGAGATCTCTAACTACA CCCAGCAGATCTATACACTGCTGGAAGAAAGTCAGAATCAGCAGGAGAAGAATA ATCAGAGCCTGCTGGCACTGGAT CNE8_HM215427_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTCCTGGTCGCCGCTGCTACACGAGTGCAT TCATCTGATAACCTGTGGGTCACCGTCTACTATGGCGTGCCAGTGTGGCGGGACG CCGATACCACACTGTTCTGCGCCAGCGACGCCAAGGCCTACGATACCGAGGTGC ACAACGTGTGGGCAACCCACGCATGCGTGCCAACAGACCCTAATCCACAGGAGA TCCACCTGGAGAACGTGACAGAGAACTTCAACATGTGGAAGAACAAGATGGCCG AGCAGATGCAGGAGGACGTGATCTCCCTGTGGGATGAGTCTCTGAAGCCCTGCG TGCAGCTGACCCCTCTGTGCGTGACACTGAATTGTACCAATGCCAACCTGAATGC CACCGTGAATGCCTCCACCACAATCGGCAACATCACAGATGAGGTGCGGAACTG TTCTTTCAATACCACAACCGAGCTGCGCGACAAGAAGCAGAACGTGTACGCCCT GTTTTATAAGCTGGATATCGTGCCCATCAACAATAACTCCGAGTATCGGCTGATC AACTGCAATACCTCTGTGATCAAGCAGGCCTGTCCTAAGGTGAGCTTCGACCCCA TCCCTATCCACTACTGCGCACCAGCAGGATATGCAATCCTGCGCTGTAATGATAA GAACTTTAATGGCACAGGCCCCTGCAAGAACGTGAGCTCCGTGCAGTGTACCCA CGGCATCAAGCCTGTGGTGTCTACACAGCTGCTGCTGAACGGCAGCCTGGCCGA GGACGAGATCATCATCAGGAGCGAGAACCTGACAGATAATGTGAAGACCATCAT CGTGCACCTGAACAAGTCCGTGGAGATCAATTGCACCAGGCCATCTAATAACAC AGTGACCAGCGTGAGAATCGGCCCCGGCCAGGTGTTCTACTATACAGGCGACAT CATCGGCGATATCCGGAAGGCCTACTGTGAGATCAATCGCACAAAGTGGCACGA GACACTGAAGCAGGTGGCCACCAAGCTGAGGGAGCACTTCAACAAGACAATCAT CTTTCAGCCCCCTTCCGGCGGCGACATCGAGATCACCATGCACCACTTCAACTGC AGAGGCGAGTTCTTTTACTGTAACACAACCAAGCTGTTTAATTCTACCTGGGGCG AGAACACAACCATGGAGGGCCACAATGATACAATCGTGCTGCCTTGCAGAATCA AGCAGATCGTGAACATGTGGCAGGGAGTGGGACAGGCAATGTATGCCCCACCCA TCAGGGGCAGCATCAACTGCGTGAGCAATATCACAGGCATCCTGCTGACCAGAG ACGGCGGAACAAACATGTCTAATGAGACATTCAGGCCTGGCGGCGGCAACATCA AGGATAATTGGAGAAGCGAGCTGTACAAGTATAAGGTGGTGGAGATCGAGCCTC TGGGCATCGCCCCAACAAAGTGCAAGAGGAGAGTGGTGGGCTCTCACAGCGGCT CCGGCGGCTCTGGCAGCGGCGGCCACGCCGCCGTGGGCATCGGCGCCATGAGCT TCGGCTTTCTGGGAGCAGCAGGCTCCACCATGGGAGCAGCCTCTATCACACTGAC CGTGCAGGCAAGGCAGCTGCTGAGCGGCATCGTGCAGCAGCAGTCCAACCTGCT GAGGGCACCAGAGCCACAGCAGCACCTGCTGCAGGACACCCACTGGGGCATCAA GCAGCTGCAGGCCCGCGTGCTGGCAGTGGAGCACTACCTGAAGGATCAGAAGTT TCTGGGCCTGTGGGGCTGTTCCGGCAAGATCATCTGCTGTACCGCCGTGCCTTGG AACTCCACATGGTCTAATCGGAGCTATGAGGAGATCTGGGACAACATGACCTGG ATCAATTGGTCCCGCGAGATCTCTAACTACACAAGCCAGATCTATGAGATCCTGA CCGAATCACAGAATCAGCAGGACAGAAACAACAAATCACTGCTGGAACTGGAC CNE55_HM215418_MD39_L14G8-nucleic acid ATGGACTGGACTTGGATTCTGTTCCTGGTCGCTGCCGCTACACGAGTGCATTCCT CTGATAAACTGTGGGTGACCGTCTACTATGGAGTGCCAGTGTGGCGGGACGCCG ATACCACACTGTTCTGCGCCTCTGACGCCAAGGCCCACGAGACAGAGGTGCACA ACGTGTGGGCAACCCACGCATGCGTGCCAACAGATCCTAACCCACAGGAGATCC ACCTGGTGAATGTGACAGAGAACTTTAATATGTGGAAGAACAAGATGGTGGAGC AGATGCAGGAGGACGTGATCAGCCTGTGGGATGAGTCCCTGAAGCCCTGCGTGA AGCTGACCCCTCTGTGCGTGACACTGAACTGTACCACAGCCAACACCAATGAGA CAAAGAACAATACCACAGACGATAATATCAAGGACGAGATGAAGAACTGTACCT TCAATATGACCACAGAGATCCGGGACAAGAAGCAGCGCGTGAGCGCCCTGTTTT ACAAGCTGGATATCGTGCCCATCGACGATAGCAAGAACAATTCCGAGTATCGCC TGATCAACTGCAATACCAGCGTGATCAAGCAGGCCTGTCCTAAGGTGTCCTTCGA CCCCATCCCTATCCACTACTGCACCCCAGCCGGCTATGTGATCCTGAAGTGTAAC GATAAGAACTTTAATGGCACAGGCCCCTGCAAGAATGTGAGCTCCGTGCAGTG ACCCACGGCATCAAGCCTGTGGTGTCCACACAGCTGCTGCTGAACGGCTCTCTGG CCGAGGAGGAGATCATCATCAGGTCTGAGAATCTGACCGATAACGCCAAGAATA TCATCGTGCACCTGAACAAGAGCGTGGAGATCAATTGCACACGGCCATCTAACA ATACCGTGACAAGCGTGCGCATCGGACCAGGACAGGTGTTCTACTATACCGGCG ACATCACAGGCGATATCAGAAAGGCCTACTGTGAGATCGACGGCACCGAGTGGA ACAAGACCCTGACACAGGTGGCCGAGAAGCTGAAGGAGCACTTTAATAAGACCA TCGTGTACCAGCCCCTTCCGGCGGCGATCTGGAGATCACAATGCACCACTTCAA CTGCCGGGGCGAGTTCTTTTATTGTAATACCACACAGCTGTTTAACAATTCTGTG GGCAACAGCACCATCAAGCTGCCTTGCCGCATCAAGCAGATCATCAATATGTGG CAGGGAGTGGGACAGGCAATGTACGCCCCACCCATCAGCGGAGCCATCAACTGT CTGTCCAATATCACCGGCATCCTGCTGACAAGGGACGGCGGCGGAAACAATAGG TCCAATGAGACATTCAGGCCTGGCGGCGGCAACATCAAGGATAATTGGAGATCT GAGCTGTACAAGTATAAGGTGGTGGAGATCGAGCCTCTGGGCATCGCCCCAACA AAGTGCAAGAGGAGAGTGGTGGGCTCTCACAGCGGCTCCGGCGGCTCTGGCAGC GGCGGCCACGCCGCCGTGGGCATCGGCGCCATGAGCTTCGGCTTTCTGGGAGCA GCAGGCTCCACCATGGGAGCAGCCTCTATCACCCTGACAGTGCAGGCCCGGCAG CTGCTGTCTGGCATCGTGCAGCAGCAGAGCAACCTGCTGAGGGCACCAGAGCCA CAGCAGCACATGCTGCAGGACACACACTGGGGCATCAAGCAGCTGCAGGCCAGG GTGCTGGCAGTGGAGCACTACCTGAAGGATCAGAGATTTCTGGGCCTGTGGGGC TGTAGCGGCAAGACCATCTGCTGTACAGCCGTGCCTTGGAACTCCACCTGGTCTA ATAAGACATATGAGGAGATCTGGGACAACATGACCTGGACAAATTGGTCCCGGG AGATCTCTAACTACACCAATCAGATCTATTCCATTCTGACCGAATCACAGTCACA GCAGGATAAAAATAACAAAAGTCTGCTGGAACTGGAT AD8_MD64_link14_TS1-nucleic acid GGATCCGCCACCATGGACTGGACTTGGATTCTGTTCCTGGTCGCCGCCGCT ACTCGGGTGCATTCTGTCGAAAACCTGTGGGTGACTGTCTATTATGGAGTGCCCG TGTGGAAGGAGGCCACCACAACCCTGTTCTGCGCCTCCGACGCCAAGGCCTACG ATACCGAGGTGCACAACGTGTGGGCCACCCACGAGTGCGTGCCTACAGACCCAA ACCCCCAGGAGGTGGTGCTGGAGAATGTGACAGAGAACTTCAACATGTGGAAGA ACAATATGGTGGAGCAGATGCACGAGGACATCATCGAGCTGTGGGATCAGAGCC TGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGACCCTGAATTGTACAGACCT GCGGAATGTGACAAACATCAACAATAGCTCCGAGGGCATGAGAGGCGAGATCAA GAATTGTAGCTTCAACATCACAACCTCCATCAGGGACAAGGTGAAGAAGGATTA CGCCCTGTTTTATCGCCTGGATGTGGTGCCCATCGACAATGATAACACCTCTTAC CGGCTGATCAATTGCAACACAAGCACCATCACACAGGCCTGTCCAAAGGTGTCCT TCGAGCCTATCCCAATCCACTATTGCACCCCCGCCGGCTTCGCCATCCTGAAGTG TAAGGACAAGAAGTTTAACGGCACAGGCCCTTGCAAGAACGTGAGCACCGTGCA GTGTACACACGGCATCCGGCCAGTGGTGAGCACCCAGCTGCTGCTGAACGGCTC CCTGGCAGAGGAGGAAGTGATCATCAGATCTAGCAATTTCACAGATAATGCCAA GAACATCATCGTGCAGCTGAAGGAGTCCGTGGAGATCAACTGCACCCGGCCCAA CAATAACACAGTGAAGTCTATCCACATCGGCCCTGGCAGAGCCTTTTACTATACC GGCGACATCATCGGCGATATCAGGCAGGCCCACTGTAACATCAGCCGCACCAAG TGGAATAACACACTGAATCAGATCGCCACCAAGCTGAAGGAGCAGTTCGGCAAT AACAAGACAATCGTGTTTAACCAGTCCTCTGGCGGCGACCCAGAGATCGTGATG CACTCTTTTAATTGCGGCGGCGAGTTCTTTTACTGTAACTCTACCCAGCTGTTCAA TAGCACATGGAACTTCAACGGCACCTGGAATCTGACACAGAGCAACGGCACCGA GGGCAATGATACCATCACACTGCCCTGCAGGATCAAGCAGATCATCAACATGTG GCAGGAAGTGGGCAAGGCCATGTATGCCCCTCCCATCAGGGGCCAGATCCGCTG TAGCTCCAATATCACCGGCCTGATCCTGACAAGGGACGGCGGAAATAACCACAA TAACGATACCGAGACATTCCGCCCCGGCGGCGGCGACATGAGGGATAACTGGAG ATCCGAGCTGTACAAGTATAAGGTGGTGAAGATCGAGCCACTGGGAGTGGCACC AACCAAGTGCAAGAGGAGAGTGGTGCAGTCTCACAGCGGCTCCGGCGGCTCTGG CAGCGGCGGCCACGCCGCCGTGGGCACCATCGGCGCCATGAGCCTGGGCTTTCT GGGAGCAGCAGGCTCCACAATGGGAGCAGCCTCTATCACCCTGACAGTGCAGGC CAGGCTGCTGCTGTCCGGCATCGTGCAGCAGCAGAATAACCTGCTGAGGGCACC AGAGCCTCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCA GGCCCGGGTGCTGGCAGTGGAGCACTATCTGAGAGATCAGCAGCTGCTGGGAAT CTGGGGATGCAGCGGCAAGCTGATCTGCTGTACCGCCGTGCCATGGAACGCCTCC TGGTCTAATAAGACCCTGGACATGATCTGGAATAACATGACATGGATGGAGTGG GAGCGCGAGATCGATAACTACACCGGCCTGATCTATACACTGATCGAGGAATCA CAGAATCAGCAGGAGAAAAACGAACAGGAACTGCTGGAACTGGATGGCGGCGT CGAAAATCTCTGGGTCACCGTCTATTATGGGGTCCCTGTCTGGAAGGAAGCAACT ACTACTCTGTTCTGTGCCTCCGATGCCAAGGCCTACGACACAGAGGTGCACAACG TGTGGGCTACACACGAGTGCGTGCCAACCGATCCAAACCCCCAGGAGGTGGTGC TGGAGAACGTGACCGAGAACTTCAACATGTGGAAGAACAACATGGTGGAGCAGA TGCACGAGGACATCATCGAGCTGTGGGATCAGTCCCTGAAGCCTTGCGTGAAGCT GACACCACTGTGCGTGACACTGAACTGTACCGACCTGAGGAACGTGACCAACAT CAACAACAGCTCCGAGGGAATGAGAGGCGAGATCAAGAACTGTAGCTTCAACAT CACCACATCCATCCGGGACAAGGTGAAGAAGGATTACGCCCTGTTTTACCGCCTG GATGTGGTGCCCATCGACAACGATAACACCTCTTACAGGCTGATCAACTGCAACA CCAGCACAATCACCCAGGCTTGTCCAAAGGTGTCCTTTGAGCCTATCCCAATCCA CTACTGCACACCCGCCGGCTTCGCTATCCTGAAGTGTAAGGACAAGAAGTTTAAC GGAACCGGCCCTTGCAAGAACGTGTCTACAGTGCAGTGTACCCACGGCATCAGG CCAGTGGTGAGCACACAGCTGCTGCTGAACGGCAGCCTGGCCGAGGAGGAAGTG ATCATCAGATCTAGCAACTTCACCGATAACGCTAAGAACATCATCGTGCAGCTGA AGGAGTCCGTGGAGATCAACTGCACAAGGCCCAACAACAACACCGTGAAGTCTA TCCACATCGGACCTGGCAGAGCCTTTTACTACACAGGAGACATCATCGGCGATAT CCGGCAGGCTCACTGTAACATCAGCCGCACAAAGTGGAACAACACCCTGAACCA GATCGCCACAAAGCTGAAGGAGCAGTTCGGCAACAACAAGACCATCGTGTTTAA CCAGTCCAGCGGCGGCGACCCCGAGATCGTGATGCACTCTTTCAACTGCGGCGG AGAGTTCTTTTACTGTAACTCTACACAGCTGTTCAACAGCACCTGGAACTTTAAC GGAACATGGAACCTGACCCAGAGCAACGGAACCGAGGGCAACGATACAATCAC CCTGCCTTGCCGGATCAAGCAGATCATCAACATGTGGCAGGAAGTGGGAAAGGC CATGTACGCTCCCCCTATCAGGGGACAGATCAGGTGTAGCTCCAACATCACAGG ACTGATCCTGACCCGGGACGGCGGAAACAACCACAACAACGATACAGAGACATT CAGGCCTGGCGGAGGCGACATGAGGGATAACTGGAGATCCGAGCTGTACAAGTA CAAGGTGGTGAAGATCGAGCCACTGGGAGTGGCTCCAACCAAGTGCAAGAGGAG AGTGGTGCAGTCTCACAGCGGCAGCGGCGGCAGCGGCAGCGGAGGCCACGCTGC TGTGGGAACAATCGGAGCTATGAGCCTGGGATTTCTGGGAGCTGCTGGCAGCAC CATGGGAGCTGCTTCTATCACACTGACCGTGCAGGCTAGGCTGCTGCTGTCCGGA ATCGTGCAGCAGCAGAACAACCTGCTGAGGGCTCCAGAGCCTCAGCAGCACCTG CTGCAGCTGACAGTGTGGGGCATCAAGCAGCTGCAGGCCAGGGTGCTGGCTGTG GAGCACTACCTGAGGGACCAGCAGCTGCTGGGCATCTGGGGATGTAGCGGCAAG CTGATCTGCTGTACCGCCGTGCCATGGAACGCTTCCTGGTCTAACAAGACACTGG ACATGATCTGGAACAACATGACCTGGATGGAGTGGGAGCGCGAGATCGATAACT ACACAGGCCTGATCTACACCCTGATCGAAGAAAGTCAGAATCAGCAGGAAAAGA ACGAACAGGAACTGCTGGAACTGGACGGTGGCGTCGAGAATCTGTGGGTCACCG TCTATTATGGAGTCCCCGTCTGGAAAGAGGCTACTACTACACTGTTTTGTGCAAG CGATGCCAAGGCCTACGACACAGAGGTGCACAACGTGTGGGCCACACACGAGTG CGTGCCAACCGATCCAAACCCCCAGGAGGTGGTGCTGGAGAATGTGACCGAGAA TTTCAACATGTGGAAGAACAATATGGTGGAGCAGATGCACGAGGACATCATCGA GCTGTGGGATCAGTCCCTGAAGCCTTGCGTGAAGCTGACACCACTGTGCGTGACA CTGAACTGTACCGACCTGAGGAATGTGACCAACATCAACAATAGCTCCGAGGGC ATGAGAGGCGAGATCAAGAATTGTAGCTTCAACATCACCACATCCATCCGGGAC AAGGTGAAGAAGGATTACGCCCTGTTTTATCGCCTGGATGTGGTGCCCATCGACA ATGATAACACCTCTTACAGGCTGATCAATTGCAACACCAGCACAATCACCCAGGC CTGTCCAAAGGTGTCCTTTGAGCCTATCCCAATCCACTATTGCACACCCGCCGGC TTCGCCATCCTGAAGTGTAAGGACAAGAAGTTTAACGGCACCGGCCCTTGCAAG AACGTGAGCACAGTGCAGTGTACCCACGGCATCAGGCCAGTGGTGAGCACACAG CTGCTGCTGAACGGCTCCCTGGCCGAGGAGGAAGTGATCATCAGATCTAGCAATT TCACCGATAATGCCAAGAACATCATCGTGCAGCTGAAGGAGTCCGTGGAGATCA ACTGCACAAGGCCCAACAATAACACCGTGAAGTCTATCCACATCGGCCCTGGCA GAGCCTTTTACTATACCGGCGACATCATCGGCGATATCCGGCAGGCCCACTGTAA CATCAGCCGCACAAAGTGGAATAACACCCTGAATCAGATCGCCACAAAGCTGAA GGAGCAGTTCGGCAATAACAAGACCATCGTGTTTAACCAGTCCTCTGGCGGCGA CCCCGAGATCGTGATGCACTCTTTCAATTGCGGCGGCGAGTTCTTTTACTGTAACT CTACACAGCTGTTCAATAGCACCTGGAACTTCAACGGCACATGGAATCTGACCCA GAGCAACGGCACCGAGGGCAATGATACAATCACCCTGCCTTGCCGGATCAAGCA GATCATCAACATGTGGCAGGAAGTGGGCAAGGCCATGTATGCCCCTCCCATCAG GGGACAGATCAGGTGTAGCTCCAATATCACAGGCCTGATCCTGACCCGGGACGG CGGAAATAACCACAATAACGATACAGAGACATTCAGGCCCGGCGGCGGCGACAT GAGGGATAACTGGAGATCCGAGCTGTACAAGTATAAGGTGGTGAAGATCGAGCC ACTGGGAGTGGCACCAACCAAGTGCAAGAGGAGAGTGGTGCAGTCTCACAGCGG CTCCGGCGGCTCTGGCAGCGGCGGCCACGCAGCAGTGGGAACAATCGGAGCAAT GAGCCTGGGCTTTCTGGGAGCAGCAGGCTCCACCATGGGAGCAGCCTCTATCAC ACTGACCGTGCAGGCAAGGCTGCTGCTGTCCGGCATCGTGCAGCAGCAGAATAA CCTGCTGAGGGCACCAGAGCCTCAGCAGCACCTGCTGCAGCTGACAGTGTGGGG CATCAAGCAGCTGCAGGCCAGGGTGCTGGCAGTGGAGCACTATCTGAGGGACCA GCAGCTGCTGGGCATCTGGGGCTGTAGCGGCAAGCTGATCTGCTGTACCGCCGTG CCCTGGAACGCCTCCTGGTCTAATAAGACACTGGACATGATCTGGAATAACATGA CCTGGATGGAGTGGGAGCGCGAGATCGATAACTACACAGGCCTGATCTATACCC TGATTGAGGAGTCACAGAACCAGCAGGAAAAGAACGAACAGGAACTGCTGGAA CTGGATTGATAACTCGAG AD8_MD64_link14-nucleic acid GGATCCGCCACCATGGACTGGACTTGGATTCTGTTCCTGGTCGCCGCCGCT ACTCGGGTGCATTCTGTCGAAAACCTGTGGGTGACTGTCTATTATGGAGTGCCCG TGTGGAAGGAGGCCACCACAACCCTGTTCTGCGCCTCCGACGCCAAGGCCTACG ATACCGAGGTGCACAACGTGTGGGCCACCCACGAGTGCGTGCCTACAGACCCAA ACCCCCAGGAGGTGGTGCTGGAGAATGTGACAGAGAACTTCAACATGTGGAAGA ACAATATGGTGGAGCAGATGCACGAGGACATCATCGAGCTGTGGGATCAGAGCC TGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGACCCTGAATTGTACAGACCT GCGGAATGTGACAAACATCAACAATAGCTCCGAGGGCATGAGAGGCGAGATCAA GAATTGTAGCTTCAACATCACAACCTCCATCAGGGACAAGGTGAAGAAGGATTA CGCCCTGTTTTATCGCCTGGATGTGGTGCCCATCGACAATGATAACACCTCTTAC CGGCTGATCAATTGCAACACAAGCACCATCACACAGGCCTGTCCAAAGGTGTCCT TCGAGCCTATCCCAATCCACTATTGCACCCCCGCCGGCTTCGCCATCCTGAAGTG TAAGGACAAGAAGTTTAACGGCACAGGCCCTTGCAAGAACGTGAGCACCGTGCA GTGTACACACGGCATCCGGCCAGTGGTGAGCACCCAGCTGCTGCTGAACGGCTC CCTGGCAGAGGAGGAAGTGATCATCAGATCTAGCAATTTCACAGATAATGCCAA GAACATCATCGTGCAGCTGAAGGAGTCCGTGGAGATCAACTGCACCCGGCCCAA CAATAACACAGTGAAGTCTATCCACATCGGCCCTGGCAGAGCCTTTTACTATACC GGCGACATCATCGGCGATATCAGGCAGGCCCACTGTAACATCAGCCGCACCAAG TGGAATAACACACTGAATCAGATCGCCACCAAGCTGAAGGAGCAGTTCGGCAAT AACAAGACAATCGTGTTTAACCAGTCCTCTGGCGGCGACCCAGAGATCGTGATG CACTCTTTTAATTGCGGCGGCGAGTTCTTTTACTGTAACTCTACCCAGCTGTTCAA TAGCACATGGAACTTCAACGGCACCTGGAATCTGACACAGAGCAACGGCACCGA GGGCAATGATACCATCACACTGCCCTGCAGGATCAAGCAGATCATCAACATGTG GCAGGAAGTGGGCAAGGCCATGTATGCCCCTCCCATCAGGGGCCAGATCCGCTG TAGCTCCAATATCACCGGCCTGATCCTGACAAGGGACGGCGGAAATAACCACAA TAACGATACCGAGACATTCCGCCCCGGCGGCGGCGACATGAGGGATAACTGGAG ATCCGAGCTGTACAAGTATAAGGTGGTGAAGATCGAGCCACTGGGAGTGGCACC AACCAAGTGCAAGAGGAGAGTGGTGCAGTCTCACAGCGGCTCCGGCGGCTCTGG CAGCGGCGGCCACGCCGCCGTGGGCACCATCGGCGCCATGAGCCTGGGCTTTCT GGGAGCAGCAGGCTCCACAATGGGAGCAGCCTCTATCACCCTGACAGTGCAGGC CAGGCTGCTGCTGTCCGGCATCGTGCAGCAGCAGAATAACCTGCTGAGGGCACC AGAGCCTCAGCAGCACCTGCTGCAGCTGACCGTGTGGGGCATCAAGCAGCTGCA GGCCCGGGTGCTGGCAGTGGAGCACTATCTGAGAGATCAGCAGCTGCTGGGAAT CTGGGGATGCAGCGGCAAGCTGATCTGCTGTACCGCCGTGCCATGGAACGCCTCC TGGTCTAATAAGACCCTGGACATGATCTGGAATAACATGACATGGATGGAGTGG GAGCGCGAGATCGATAACTACACCGGCCTGATCTATACACTGATCGAGGAATCA CAGAATCAGCAGGAGAAAAACGAACAGGAACTGCTGGAACTGGATTGATAACTC GAG 001428_MD39_link14_TS1-nucleic acid GGATCCGCCACCATGGACTGGACTTGGATTCTGTTCCTGGTGGCAGCAGC AACTAGAGTGCATTCCGTCGAAAACCTGTGGGTGACCGTGTATTATGGAGTGCCC GTGTGGAAGGAGGCCCGGACCACACTGTTCTGCGCCTCCGACGCCAAGGCCTAC GAGACAGAGGTGCACAACGTGTGGGCCACACACGCCTGCGTGCCTACCGATCCA AATCCCCAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTTAATATGTGGAAG AACGACATGGTGGATCAGATGCACGAGGACGTGATCTCTCTGTGGGCCCAGAGC CTGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGG TGAACGCCACACAGGGCAATACCACACAGGTGAACGTGACCCAAGTGAATGGCG ACGAGATGAAGAACTGTTCCTTCAATACCACAACCGAGATCCGGGATAAGAAGC AGAAGGCCTACGCCCTGTTTTATAGACTGGACCTGGTGCCTCTGGAGCGGGAGA ACAGAGGCGATTCTAATAGCGCCTCCAAGTATATCCTGATCAACTGCAATACATC TGCCATCACCCAGGCCTGTCCTAAAGTGAATTTCGATCCTATCCCAATCCACTAC TGCACCCCAGCCGGCTATGCCATCCTGAAGTGTAACAACAAGACCTTCAACGGC ACCGGCTCCTGCAACAACGTGAGCACAGTGCAGTGTACCCACGGCATCAAGCCA GTGGTGAGCACCCAGCTGCTGCTGAACGGCTCCCTGGCAGAGGAGGAGATCATC ATCAGGTCCGAGAACCTGACAGACAATGTGAAGACCATCATCGTGCACCTGGAT CAGTCCGTGGAGATCGTGTGCACACGGCCAAACAATAACACCGTGAAGTCTATC AGAATCGGCCCCGGCCAGACATTCTACTATACCGGCGACATCATCGGCAATATCC GGGAGGCCCACTGTAACATCTCTGAGAAGAAGTGGCACGAGATGCTGCGGAGAG TGAGCGAGAAGCTGGCCGAGCACTTCCCCAATAAGACAATCAAGTTTACCAGCT CCTCTGGCGGCGATCTGGAGATCACAACCCACAGCTTCAACTGCAGAGGCGAGT TCTTTTACTGTAACACCAGCGGCCTGTTTAATTCCACATACATGCCCAACGGCAC CTATATGCCTAATGGCACAAATAACTCTAACAGCACCATCATCCTGCCATGCCGG ATCAAGCAGATCATCAATATGTGGCAGGAAGTGGGCAGAGCCATGTATGCCCCT CCCATCGCCGGCAACATCACATGTAACAGCAATATCACCGGCCTGCTGCTGGTGA GGGACGGCGGCAAGAATAACAATACAGAGATCTTCCGCCCCGGCGGCGGCGACA TGAGGGATAACTGGCGCTCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGC CACTGGGAGTGGCACCAACCAGGTGCAAGAGGCGCGTGGTGGGCTCCCACTCTG GCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCAGTGGGCCTGGGAGCCGTGA GCCTGGGCTTTCTGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAGCATCACAC TGACCGTGCAGGCAAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCAGTCTAACC TGCTGCAGGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCA TCAAGCAGCTGCAGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGC AGCTGCTGGGCATCTGGGGCTGCTCTGGCAAGCTGATCTGCTGTACAGCCGTGCC TTGGAACAGCTCCTGGAGCAATAAGTCCCTGACAGACATCTGGGATAATATGAC CTGGATGCAGTGGGATAGGGAGGTGAGCAACTACACCGGCATCATCTATCGCCT GCTGGAAGACTCACAGAATCAGCAGGAAAGGAATGAACAGGATCTGCTGGCACT GGACGGGGGAGTCGAGAACCTCTGGGTCACCGTGTATTATGGAGTCCCCGTCTG GAAAGAAGCCCGAACCACCCTGTTTTGTGCCTCTGATGCTAAAGCCTACGAGACA GAGGTGCACAACGTGTGGGCTACACACGCTTGCGTGCCAACCGACCCAAACCCC CAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAAGAACGAC ATGGTGGATCAGATGCACGAGGATGTGATCTCTCTGTGGGCCCAGAGCCTGAAG CCTTGCGTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGGTGAACG CTACACAGGGCAACACCACACAGGTGAACGTGACCCAGGTGAACGGAGACGAG ATGAAGAACTGTTCCTTCAACACCACAACCGAGATCAGGGATAAGAAGCAGAAG GCCTACGCTCTGTTTTACAGACTGGACCTGGTGCCACTGGAGAGGGAGAACAGA GGCGATTCTAACAGCGCCTCCAAGTACATCCTGATCAACTGCAACACATCTGCCA TCACCCAGGCTTGTCCTAAGGTGAACTTCGACCCTATCCCAATCCACTACTGCAC ACCAGCCGGCTACGCTATCCTGAAGTGTAACAACAAGACCTTCAACGGAACCGG CTCCTGCAACAACGTGTCTACAGTGCAGTGTACCCACGGCATCAAGCCCGTGGTG AGCACCCAGCTGCTGCTGAACGGCAGCCTGGCTGAGGAGGAGATCATCATCCGG TCCGAGAACCTGACAGACAACGTGAAGACCATCATCGTGCACCTGGATCAGTCC GTGGAGATCGTGTGCACAAGGCCAAACAACAACACCGTGAAGTCTATCAGAATC GGACCCGGCCAGACCTTCTACTACACCGGAGACATCATCGGCAACATCAGGGAG GCCCACTGTAACATCTCTGAGAAGAAGTGGCACGAGATGCTGAGGAGAGTGAGC GAGAAGCTGGCTGAGCACTTCCCTAACAAGACAATCAAGTTTACCAGCTCCTCTG GCGGAGATCTGGAGATCACAACCCACAGCTTCAACTGCAGAGGAGAGTTCTTTT ACTGTAACACCAGCGGCCTGTTTAACTCCACATACATGCCCAACGGAACCTACAT GCCTAACGGCACAAACAACTCTAACAGCACCATCATCCTGCCCTGCAGGATCAA GCAGATCATCAACATGTGGCAGGAAGTGGGAAGAGCCATGTACGCTCCCCCTAT CGCCGGCAACATCACATGTAACAGCAACATCACCGGACTGCTGCTGGTGCGGGA CGGCGGAAAGAACAACAACACAGAGATCTTCCGCCCTGGCGGAGGCGACATGAG GGATAACTGGCGCTCCGAGCTGTACAAGTACAAGGTGGTGGAGATCAAGCCACT GGGAGTGGCTCCAACCAGGTGCAAGAGGAGGGTGGTGGGCAGCCACTCTGGCAG CGGAGGCTCCGGATCTGGAGGCCACGCTGCTGTGGGACTGGGAGCCGTGAGCCT GGGATTTCTGGGAGCTGCTGGATCTACCATGGGAGCTGCTAGCATCACACTGACC GTGCAGGCTAGGCAGCTGCTGTCCGGAATCGTGCAGCAGCAGTCTAACCTGCTGC AGGCTCCCGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCATCAAGC AGCTGCAGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCAGCTGC TGGGCATCTGGGGATGTTCTGGCAAGCTGATCTGCTGTACAGCTGTGCCATGGAA CAGCTCCTGGAGCAACAAGTCCCTGACAGACATCTGGGATAACATGACCTGGAT GCAGTGGGATCGGGAGGTGAGCAACTACACCGGCATCATCTACCGCCTGCTGGA AGACTCACAGAATCAGCAGGAACGGAATGAACAGGACCTCCTCGCCTGGATGG CGGAGTCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCAGTGTGGAAAGA GGCTAGGACTACCCTGTTCTGTGCCAGCGATGCCAAAGCCTACGAGACAGAGGT GCACAACGTGTGGGCAACACACGCATGCGTGCCAACCGACCCAAATCCCCAGGA GATGGTGCTGGGCAACGTGACCGAGAACTTCAATATGTGGAAGAACGACATGGT GGATCAGATGCACGAGGATGTGATCTCTCTGTGGGCCCAGAGCCTGAAGCCTTGC GTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGGTGAACGCCACA CAGGGCAATACCACACAGGTGAACGTGACCCAAGTGAATGGCGACGAGATGAA GAACTGTTCCTTCAATACCACAACCGAGATCAGGGATAAGAAGCAGAAGGCCTA CGCCCTGTTTTATAGACTGGACCTGGTGCCACTGGAGAGGGAGAACAGAGGCGA TTCTAATAGCGCCTCCAAGTATATCCTGATCAACTGCAATACATCTGCCATCACC CAGGCCTGTCCTAAAGTGAATTTCGACCCTATCCCAATCCACTACTGCACACCAG CCGGCTATGCCATCCTGAAGTGTAACAACAAGACCTTCAACGGCACCGGCTCCTG CAACAACGTGAGCACAGTGCAGTGACCCACGGCATCAAGCCCGTGGTGAGCAC CCAGCTGCTGCTGAACGGCTCCCTGGCAGAGGAGGAGATCATCATCCGGTCCGA GAACCTGACAGACAATGTGAAGACCATCATCGTGCACCTGGATCAGTCCGTGGA GATCGTGTGCACAAGGCCAAACAATAACACCGTGAAGTCTATCAGAATCGGCCC CGGCCAGACCTTCTACTATACCGGCGACATCATCGGCAATATCAGGGAGGCCCA CTGTAACATCTCTGAGAAGAAGTGGCACGAGATGCTGAGGAGAGTGAGCGAGAA GCTGGCCGAGCACTTCCCTAATAAGACAATCAAGTTTACCAGCTCCTCTGGCGGC GATCTGGAGATCACAACCCACAGCTTCAACTGCAGCGGCGAGTTCTTTTACTGTA ACACCAGCGGCCTGTTTAATTCCACATACATGCCCAACGGCACCTATATGCCTAA TGGCACAAATAACTCTAACAGCACCATCATCCTGCCCTGCAGGATCAAGCAGATC ATCAATATGTGGCAGGAAGTGGGCAGAGCCATGTATGCCCCTCCCATCGCCGGC AACATCACATGTAACAGCAATATCACCGGCCTGCTGCTGGTGCGGGACCGGCGGC AAGAATAACAATACAGAGATCTTCCGCCCCGGCGGCGGCGACATGAGGGATAAC TGGCGCTCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGCCACTGGGAGTG GCACCAACCAGGTGCAAGAGGCGCGTGGTGGGCTCCCACTCTGGCAGCGGCGGC TCCGGCTCTGGCGGCCACGCAGCAGTGGGCCTGGGAGCCGTGTCCCTGGGCTTTC TGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAGCATCACACTGACCGTGCAGG CAAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCAGTCTAACCTGCTGCAGGCAC CAGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCATCAAGCAGCTGC AGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCAGCTGCTGGGCA TCTGGGGCTGTTCTGGCAAGCTGATCTGCTGTACAGCCGTGCCATGGAACAGCTC CTGGAGCAATAAGTCCCTGACAGACATCTGGGATAATATGACCTGGATGCAGTG GGATCGGGAGGTGAGCAACTACACCGGCATCATCTATCGCCTGCTGGAGGACTC ACAGAATCAGCAGGAGCGGAACGAACAGGATCTGCTGGCACTGGATTGATAACT CGAG 001428_MD39_link14-nucleic acid GGATCCGCCACCATGGACTGGACTTGGATTCTGTTCCTGGTGGCAGCAGC AACTAGAGTGCATTCCGTCGAAAACCTGTGGGTGACCGTGTATTATGGAGTGCCC GTGTGGAAGGAGGCCCGGACCACACTGTTCTGCGCCTCCGACGCCAAGGCCTAC GAGACAGAGGTGCACAACGTGTGGGCCACACACGCCTGCGTGCCTACCGATCCA AATCCCCAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTTAATATGTGGAAG AACGACATGGTGGATCAGATGCACGAGGACGTGATCTCTCTGTGGGCCCAGAGC CTGAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGG TGAACGCCACACAGGGCAATACCACACAGGTGAACGTGACCCAAGTGAATGGCG ACGAGATGAAGAACTGTTCCTTCAATACCACAACCGAGATCCGGGATAAGAAGC AGAAGGCCTACGCCCTGTTTTATAGACTGGACCTGGTGCCTCTGGAGCGGGAGA ACAGAGGCGATTCTAATAGCGCCTCCAAGTATATCCTGATCAACTGCAATACATC TGCCATCACCCAGGCCTGTCCTAAAGTGAATTTCGATCCTATCCCAATCCACTAC TGCACCCCAGCCGGCTATGCCATCCTGAAGTGTAACAACAAGACCTTCAACGGC ACCGGCTCCTGCAACAACGTGAGCACAGTGCAGTGTACCCACGGCATCAAGCCA GTGGTGAGCACCCAGCTGCTGCTGAACGGCTCCCTGGCAGAGGAGGAGATCATC ATCAGGTCCGAGAACCTGACAGACAATGTGAAGACCATCATCGTGCACCTGGAT CAGTCCGTGGAGATCGTGTGCACACGGCCAAACAATAACACCGTGAAGTCTATC AGAATCGGCCCCGGCCAGACATTCTACTATACCGGCGACATCATCGGCAATATCC GGGAGGCCCACTGTAACATCTCTGAGAAGAAGTGGCACGAGATGCTGCGGAGAG TGAGCGAGAAGCTGGCCGAGCACTTCCCCAATAAGACAATCAAGTTTACCAGCT CCTCTGGCGGCGATCTGGAGATCACAACCCACAGCTTCAACTGCAGAGGCGAGT TCTTTTACTGTAACACCAGCGGCCTGTTTAATTCCACATACATGCCCAACGGCAC CTATATGCCTAATGGCACAAATAACTCTAACAGCACCATCATCCTGCCATGCCGG ATCAAGCAGATCATCAATATGTGGCAGGAAGTGGGCAGAGCCATGTATGCCCCT CCCATCGCCGGCAACATCACATGTAACAGCAATATCACCGGCCTGCTGCTGGTGA GGGACGGCGGCAAGAATAACAATACAGAGATCTTCCGCCCCGGCGGCGGCGACA TGAGGGATAACTGGCGCTCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGC CACTGGGAGTGGCACCAACCAGGTGCAAGAGGCGCGTGGTGGGCTCCCACTCTG GCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCAGTGGGCCTGGGAGCCGTGA GCCTGGGCTTTCTGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAGCATCACAC TGACCGTGCAGGCAAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCAGTCTAACC TGCTGCAGGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCA TCAAGCAGCTGCAGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGC AGCTGCTGGGCATCTGGGGCTGCTCTGGCAAGCTGATCTGCTGTACAGCCGTGCC TTGGAACAGCTCCTGGAGCAATAAGTCCCTGACAGACATCTGGGATAATATGAC CTGGATGCAGTGGGATAGGGAGGTGAGCAACTACACCGGCATCATCTATCGCCT GCTGGAAGACTCACAGAATCAGCAGGAAAGGAATGAACAGGATCTGCTGGCACT GGACTGATAACTCGAG

The disclosure relates to a composition comprising one or more nucleic acid molecules. The composition can comprise one, two, three or more nucleic acid molecules, each nucleic acid molecule comprising at least a first expressible nucleic acid sequence comprising at least one nucleic acid sequence that encodes a retroviral monomer or retorviral trimer peptide, the trimer peptide comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to one or combination of amino acid sequences selected from: SEQ ID NO: 55, SEQ ID NO: 58, SEQ ID NO: 61, SEQ ID NO: 64, SEQ ID NO: 80, SEQ ID NO: 83, SEQ ID NO: 86, SEQ ID NO: 89, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 126, SEQ ID NO: 129, SEQ ID NO: 132 or pharmaceutically acceptable salts thereof.

In some embodiments, upon administration to a subject, the composition comprising a nucleic acid comprising the expressible nucleic acid sequence is transfected or transduced into an antigen presenting cell which encodes the expressible nucleic acid sequence. After a plurality of expressible nucleic acid sequences are encoded, the first, second and third polypeptides assemble into a trimer comprising a secondary structure that exposes one or a plurality of epitopes that are not naturally exposed when the polypeptides or variants thereof are expressed under normal conditions and naturally in a host cell. Antigen presenting cells expressing the one or plurality of viral antigens can elicit a therapeutically effective antigen-specific immune response against the virus in a subject. For example, in some embodiments, the viral antigen can be an antigen from human immunodeficiency virus-1 (HIV-1).

In some embodiments, the nucleic acid sequence is an RNA sequence. In some embodiments, the RNA sequence according to the present disclosure comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more sequence identity to one or combination of RNA sequences provided in Table Y. In some embodiments, the RNA sequence according to the present disclosure comprises one or combination of RNA sequences provided in Table Y. In some embodiments, the RNA sequence according to the present disclosure comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more sequence identity to one or combination of RNA sequences selected from: SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO:256, SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265 or pharmaceutically acceptable salts thereof. In some embodiments, the RNA sequence according to the present disclosure comprises one or combination of RNA sequences selected from: SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO:256, SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265 or pharmaceutically acceptable salts thereof.

5. Regulatory Sequences

In some embodiments, the expressible nucleic acid sequence can be operably linked to one or a plurality of regulatory sequences. The term “regulatory sequence” as used herein refer to DNA sequences which are necessary to effect expression of sequences to which they are ligated. The term “regulatory sequence” is intended to include, as a minimum, all components necessary for expression and optionally additional advantageous components. In some embodiments, the regulatory sequence is a promoter sequence. As used herein, a “promoter” means a region of DNA upstream from the transcription start and which is involved in binding RNA polymerase and other proteins to start transcription. Reference herein to a “promoter” is to be taken in its broadest context and includes the transcriptional regulatory sequences derived from a classical eukaryotic genomic gene, including the TATA box which is required for accurate transcription initiation, with or without a CCAAT box sequence and additional regulatory elements (i.e. upstream activating sequences, enhancers and silencers) which alter gene expression in response to developmental and/or external stimuli, or in a tissue-specific manner. Consequently, a repressible promoter's rate of transcription decreases in response to a repressing agent. An inducible promoter's rate of transcription increases in response to an inducing agent. A constitutive promoter's rate of transcription is not specifically regulated, though it can vary under the influence of general metabolic conditions. The term “promoter” also includes the transcriptional regulatory sequences of a classical prokaryotic gene, in which case it may include a −35 box sequence and/or a −10 box transcriptional regulatory sequences. The term “promoter” is also used to describe a synthetic or fusion molecule, or derivative which confers, activates or enhances expression of a nucleic acid molecule in a cell, tissue or organ.

6. Nucleic Acid Molecule

In some embodiments, the disclosed compositions further comprise a nucleic acid molecule that comprises the expressible nucleic acid sequences. For example, the nucleic acid molecule can be a plasmid. Provided herein is a vector or plasmid that is capable of expressing a at least one soluble trimer of a retroviral envelope polypeptide or constructs in the cell of a mammal in a quantity effective to elicit an immune response in the mammal. The vector may comprise heterologous nucleic acid encoding the one or more viral antigens (such as HIV-1 antigens). In some embodiments, the nucleic acid expresses a trimer of gp120, gp 41, gp160 or pharmaceutically acceptable salts or functional fragments thereof. The vector may be a plasmid. The plasmid may be useful for transfecting cells with nucleic acid encoding a viral antigen, which the transformed host cell is cultured and maintained under conditions wherein expression of the viral antigen takes place and wherein the structure of the trimer elicits an immune response of a magnitude greater than and/or more therapeutically effective than the immune response elicited by the antigen alone. The plasmid may further comprise an initiation codon, which may be upstream of the expressible sequence, and a stop codon, which may be downstream of the coding sequence. The initiation and termination codon may be in frame with the expressible sequence.

The plasmid may also comprise a promoter that is operably linked to the coding sequence. The promoter operably linked to the coding sequence may be a promoter from simian virus 40 (SV40), a mouse mammary tumor virus (MMTV) promoter, a human immunodeficiency virus (HIV) promoter such as the bovine immunodeficiency virus (BIV) long terminal repeat (LTR) promoter, a Moloney virus promoter, an avian leukosis virus (ALV) promoter, a cytomegalovirus (CMV) promoter such as the CMV immediate early promoter, Epstein Barr virus (EBV) promoter, or a Rous sarcoma virus (RSV) promoter. The promoter may also be a promoter from a human gene such as human actin, human myosin, human hemoglobin, human muscle creatine, or human metalothionein. The promoter may also be a tissue specific promoter, such as a muscle or skin specific promoter, natural or synthetic. Examples of such promoters are described in US patent application publication no. US20040175727, the contents of which are incorporated herein in its entirety. The plasmid may also comprise a polyadenylation signal, which may be downstream of the coding sequence. The polyadenylation signal may be a SV40 polyadenylation signal, LTR polyadenylation signal, bovine growth hormone (bGH) polyadenylation signal, human growth hormone (hGH) polyadenylation signal, or human β-globin polyadenylation signal. The SV40 polyadenylation signal may be a polyadenylation signal from a pCEP4 plasmid (Invitrogen, San Diego, Calif.).

The plasmid may also comprise an enhancer upstream of the coding sequence. The enhancer may be human actin, human myosin, human hemoglobin, human muscle creatine or a viral enhancer such as one from CMV, FMDV, RSV or EBV. Polynucleotide function enhancers are described in U.S. Pat. Nos. 5,593,972, 5,962,428, and WO94/016737, the contents of each are fully incorporated by reference. The plasmid may also comprise a mammalian origin of replication in order to maintain the plasmid extrachromosomally and produce multiple copies of the plasmid in a cell. The plasmid may be pVAX1, pCEP4 or pREP4 from ThermoFisher Scientific (San Diego, Calif.), which may comprise the Epstein Barr virus origin of replication and nuclear antigen EBNA-1 coding region, which may produce high copy episomal replication without integration. The vector can be pVAX1 or a pVax1 variant with changes such as the variant plasmid described herein. The variant pVax1 plasmid is a 2998 basepair variant of the backbone vector plasmid pVAX1 (Invitrogen, Carlsbad Calif.). The CMV promoter is located at bases 137-724. The 17 promoter/priming site is at bases 664-683. Multiple cloning sites are at bases 696-811. Bovine GH polyadenylation signal is at bases 829-1053. The Kanamycin resistance gene is at bases 1226-2020. The pUC origin is at bases 2320-2993. The vaccine may comprise the consensus antigens and plasmids at quantities of from about 1 nanogram to 100 milligrams; about 1 microgram to about 10 milligrams; or preferably about 0.1 microgram to about 10 milligrams; or more preferably about 1 milligram to about 2 milligram. In some embodiments, pharmaceutical compositions according to the present invention comprise from about 1 nanogram to about 1000 micrograms of DNA, The pVAX1 plasmid sequence is as follows:

(SEQ ID NO: 229) gactcttcgcgatgtacgggccagatatacgcgtt gacattgattattgactagttattaatagtaatca attacggggtcattagttcatagcccatatatgga gttccgcgttacataacttacggtaaatggcccgc ctggctgaccgcccaacgacccccgcccattgacg tcaataatgacgtatgttcccatagtaacgccaat agggactttccattgacgtcaatgggtggactatt tacggtaaactgcccacttggcagtacatcaagtg tatcatatgccaagtacgccccctattgacgtcaa tgacggtaaatggcccgcctggcattatgcccagt acatgaccttatgggactttcctacttggcagtac atctacgtattagtcatcgctattaccatggtgat gcggttttggcagtacatcaatgggcgtggatagc ggtttgactcacggggatttccaagtctccacccc attgacgtcaatgggagtttgttttggcaccaaaa tcaacgggactttccaaaatgtcgtaacaactccg ccccattgacgcaaatgggcggtaggcgtgtacgg tgggaggtctatataagcagagctctctggctaac tagagaacccactgcttactggcttatcgaaatta atacgactcactatagggagacccaagctggctag cgtttaaacttaagcttggtaccgagctcggatcc actagtccagtgtggtggaattctgcagatatcca gcacagtggcggccgctcgagtctagagggcccgt ttaaacccgctgatcagcctcgactgtgccttcta gttgccagccatctgttgtttgcccctcccccgtg ccttccttgaccctggaaggtgccactcccactgt cctttcctaataaaatgaggaaattgcatcgcatt gtctgagtaggtgtcattctattctggggggtggg gtggggcaggacagcaagggggaggattgggaaga caatagcaggcatgctggggatgcggtgggctcta tggcttctactgggcggttttatggacagcaagcg aaccggaattgccagctggggcgccctctggtaag gttgggaagccctgcaaagtaaactggatggcttt ctcgccgccaaggatctgatggcgcaggggatcaa gctctgatcaagagacaggatgaggatcgtttcgc atgattgaacaagatggattgcacgcaggttctcc ggccgcttgggtggagaggctattcggctatgact gggcacaacagacaatcggctgctctgatgccgcc gtgttccggctgtcagcgcaggggcgcccggttct ttttgtcaagaccgacctgtccggtgccctgaatg aactgcaagacgaggcagcgcggctatcgtggctg gccacgacgggcgttccttgcgcagctgtgctcga cgttgtcactgaagcgggaagggactggctgctat tgggcgaagtgccggggcaggatctcctgtcatct caccttgctcctgccgagaaagtatccatcatggc tgatgcaatgcggcggctgcatacgcttgatccgg ctacctgcccattcgaccaccaagcgaaacatcgc atcgagcgagcacgtactcggatggaagccggtct tgtcgatcaggatgatctggacgaagagcatcagg ggctcgcgccagccgaactgttcgccaggctcaag gcgagcatgcccgacggcgaggatctcgtcgtgac ccatggcgatgcctgcttgccgaatatcatggtgg aaaatggccgcttttctggattcatcgactgtggc cggctgggtgtggcggaccgctatcaggacatagc gttggctacccgtgatattgctgaagagcttggcg gcgaatgggctgaccgcttcctcgtgctttacggt atcgccgctcccgattcgcagcgcatcgccttcta tcgccttcttgacgagttcttctgaattattaacg cttacaatttcctgatgcggtattttctccttacg catctgtgcggtatttcacaccgcatacaggtggc acttttcggggaaatgtgcgcggaacccctatttg tttatttttctaaatacattcaaatatgtatccgc tcatgagacaataaccctgataaatgcttcaataa tagcacgtgctaaaacttcatttttaatttaaaag gatctaggtgaagatcctttttgataatctcatga ccaaaatcccttaacgtgagttttcgttccactga gcgtcagaccccgtagaaaagatcaaaggatcttc ttgagatcctttttttctgcgcgtaatctgctgct tgcaaacaaaaaaaccaccgctaccagcggtggtt tgtttgccggatcaagagctaccaactctttttcc gaaggtaactggcttcagcagagcgcagataccaa atactgtccttctagtgtagccgtagttaggccac cacttcaagaactctgtagcaccgcctacatacct cgctctgctaatcctgttaccagtggctgctgcca gtggcgataagtcgtgtcttaccgggttggactca agacgatagttaccggataaggcgcagcggtcggg ctgaacggggggttcgtgcacacagcccagcttgg agcgaacgacctacaccgaactgagatacctacag cgtgagctatgagaaagcgccacgcttcccgaagg gagaaaggcggacaggtatccggtaagcggcaggg tcggaacaggagagcgcacgagggagcttccaggg ggaaacgcctggtatctttatagtcctgtcgggtt tcgccacctctgacttgagcgtcgatttttgtgat gctcgtcaggggggcggagcctatggaaaaacgcc agcaacgcggcctttttacggttcctgggcttttg ctggccttttgctcacatgttctt

In some embodiments, the disclosure relates to a plasmid comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 229, the plasmid comprising an expressible nucleic acid sequence within the multiple cloning site, and the expressible nucleic acid sequence comprising one or combination of nucleic acid sequences selected from: SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 226, SEQ ID NO: 227, pharmaceutically acceptable salts thereof; or nucleic acid sequences that comprise at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one or combination of nucleic acid sequences disclosed from SEQ ID NO: 53 through SEQ ID NO: 131.

In some embodiments, the plasmid comprises an expressible nucleic acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO: 239 or a pharmaceutically acceptable salt thereof.

(SEQ ID NO: 239) ATGGACTGGACCTGGATTCTGTTCCTGGTGGCCGC CGCCACAAGGGTGCACAGCATGCAGATCTACGAAG GAAAACTGACCGCTGAGGGACTGAGGTTCGGAATT GTCGCAAGCCGCGCGAATCACGCACTGGTGGATAG GCTGGTGGAAGGCGCTATCGACGCAATTGTCCGGC ACGGCGGGAGAGAGGAAGACATCACACTGGTGAGA GTCTGCGGCAGCTGGGAGATTCCCGTGGCAGCTGG AGAACTGGCTCGAAAGGAGGACATCGATGCCGTGA TCGCTATTGGGGTCCTGTGCCGAGGAGCAACTCCC AGCTTCGACTACATCGCCTCAGAAGTGAGCAAGGG GCTGGCTGATCTGTCCCTGGAGCTGAGGAAACCTA TCACTTTTGGCGTGATTACTGCCGACACCCTGGAA CAGGCAATCGAGGCGGCCGGCACCTGCCATGGAAA CAAAGGCTGGGAAGCAGCCCTGTGCGCTATTGAGA TGGCAAATCTGTTCAAATCTCTGCGAGGAGGCTCC GGAGGATCTGGAGGGAGTGGAGGCTCAGGAGGAGG CGACACCATCACACTGCCATGCCGCCCTGCACCAC CTCCACATTGTAGCTCCAACATCACCGGCCTGATT CTGACAAGACAGGGGGGATATAGTAACGATAATAC CGTGATTTTCAGGCCCTCAGGAGGGGACTGGAGGG ACATCGCACGATGCCAGATTGCTGGAACAGTGGTC TCTACTCAGCTGTTTCTGAACGGCAGTCTGGCTGA GGAAGAGGTGGTCATCCGATCTGAAGACTGGCGGG ATAATGCAAAGTCAATTTGTGTGCAGCTGAACACA AGCGTCGAGATCAATTGCACTGGCGCAGGGCACTG TAACATTTCTCGGGCCAAATGGAACAATACCCTGA AGCAGATCGCCAGTAAACTGAGAGAGCAGTACGGC AATAAGACAATCATCTTCAAGCCTTCTAGTGGAGG CGACCCAGAGTTCGTGAACCATAGCTTTAATTGCG GGGGAGAGTTCTTTTATTGTGATTCCACACAGCTG TTCAACAGCACTTGGTTTAATTCCACCTGATAA

Thus, in some embodiments, the disclosed compositions can be vectors comprising a DNA backbone with an expressible insert comprising one or more of the disclosed leader sequences, self-assembling polypeptides, linkers and/or viral antigens.

The disclosure relates to a nucleic acid sequence comprising at least one expressible nucleic acid sequence comprising in a 5′ to 3′ orientation, a leader sequence, retroviral trimer sequence and, optionally, a transmembrane domain. The disclosure relates to a nucleic acid sequence comprising at least one expressible nucleic acid sequence comprising in a 5′ to 3′ orientation, a leader sequence, retroviral trimer sequence and, optionally, a foldon domain. In some embodiments, the at least one expressible nucleic acid sequence comprising in a 5′ to 3′ orientation, a leader sequence, retroviral trimer sequence and, optionally, a transmembrane domain and a foldon domain. In some embodiments, the transmembrane membrane domain encodes a platelet derived growth factor receptor or functional fragment thereof that comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to

(SEQ ID NO: 240) AVGQDTQEVIVVPHSLPFKVVVISAILALVVLTI ISLIILIMLWQKKPR.

In some embodiments, the expressible nucleic acid encodes a foldon domain or functional fragment thereof that comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to

(SEQ ID NO: 235) YIPEAPRDGQAYVRKDGEWVLLSTFL.

The disclosure also relates to a composition (such as a pharmaceutical composition) comprising a nucleic acid molecule comprising at least one nucleic acid expressible nucleic acid sequence that encodes one or more retorviral monomers. In some embodiments, the nucleic acid molecule comprises at least a first nucleic acid sequence comprising a first, second, a third domain, each domain encoding a retroviral monomer, and each monomer independently selected from: an amino acid or functional fragment thereof that comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to those amino acids from, through and between SEQ ID NO: 55 through SEQ ID NO: 132.

In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to those amino acids from, through and between SEQ ID NO: 156 through SEQ ID NO: 228. In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to a sequence identified as a sequence MD39. In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to BG505. In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to a sequence identified as a sequence TRO11. In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to a sequence identified as a sequence AY835445. In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, the sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to a sequence identified as a sequence X2278.

In some embodiments, the composition comprises an expressible nucleic acid sequence comprising three retroviral monomer sequences, a first monomer sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to SEQ ID NO: 55 through SEQ ID NO: 228, a second monomer encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to SEQ ID NO: 156 through SEQ ID NO: 228, and a third monomer sequence encoding an amino acid sequence or functional fragment that is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to SEQ ID NO: 55 through SEQ ID NO: 228. In some embodiments, each of the retorviral monomer sequences are linked by one or more linker sequences.

In some embodiments, the composition is a pharmaceutical composition comprising SEQ ID NO identified as a leader and a nucleic acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% or 100% sequence identity or sequence homology to a nucleic acid sequence from, through and between SEQ ID NO: 53 to SEQ ID NO: 228, wherein, within the multiple cloning site the nucleic acid molecule further comprise at least on expressible nucleic acid sequence operably linked to a promoter sequence, the expressible nucleic acid sequence comprising:

(i) one or a combination of nucleic acid sequences chosen from a leader sequence disclosed herein; or

(ii) one or a combination of nucleic acid sequences wherein the at least one nucleic acid sequence comprises at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to a sequence chosen from: SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 226, SEQ ID NO: 227; or

(iii) one or a combination of nucleic acid sequences that encode an amino acid sequence chosen from: SEQ ID NO: 55, SEQ ID NO: 58, SEQ ID NO: 61, SEQ ID NO: 64, SEQ ID NO: 80, SEQ ID NO: 83, SEQ ID NO: 86, SEQ ID NO: 89, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 126, SEQ ID NO: 129, SEQ ID NO: 132; or

(iv) one or a combination of nucleic acid sequences that encode at least one amino acid sequences comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to a sequence chosen from: a linker sequence disclosed herein.

In some embodiments, the expressible nucleic acid sequence comprises RNA. Exemplary RNA sequences of the disclosure are one or a combination of nucleic acid sequences that comprise at least about 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100% sequence identity to a sequence chosen from:

BG505_SOSIP_MD39_trimer string 1-RNA (SEQ ID NO: 241) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGC CGCUACAAGAGUGCAUUCCGCCGAAAACCUGUGGG UCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGAC GCCGAGACUACGCUGUUCUGCGCCAGCGAUGCCAA GGCCUACGAGACAGAGAAGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCUACAGACCCAAACCCCCAG GAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAG CCCUGCGUGAAGCUGACCCCUCUGUGCGUGACACU GCAGUGUACCAACGUGACAAACAAUAUCACCGACG AUAUGCGGGGCGAGCUGAAGAAUUGUAGCUUCAAC AUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGU GUACUCCCUGUUUUAUAGACUGGAUGUGGUGCAGA UCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGC AACAAGGAGUACCGCCUGAUCAAUUGCAACACCUC CGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCG AGCCUAUCCCAAUCCACUAUUGCGCCCCAGCCGGC UUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAA CGGAACCGGACCAUGCCCUUCCGUGUCUACCGUGC AGUGUACACACGGCAUCAAGCCUGUGGUGUCUACA CAGCUGCUGCUGAAUGGCAGCCUGGCCGAGGAGGA AGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUG CCAAGAAUAUCCUGGUGCAGCUGAACACACCAGUG CAGAUCAAUUGCACCCGGCCCAACAAUAACACAGU GAAGUCUAUCCGCAUCGGCCCAGGCCAGGCCUUUU ACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAG GCCCACUGUAAUGUGAGCAAGGCCACCUGGAACGA GACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGC ACUUCGGCAAUAACACCAUCAUCAGAUUUGCACAG AGCUCCGGCGGCGACCUGGAGGUGACCACACACUC CUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAACA CAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAAC ACAUCUGUGCAGGGCAGCAAUUCCACCGGCAGCAA CGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGA UCAUCAACAUGUGGCAGCGCAUCGGCCAGGCCAUG UAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGU GAGCAAUAUCACCGGCCUGAUCCUGACACGCGACG GCGGCUCUACCAACAGCACCACAGAGACAUUCCGG CCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUC UGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGC CUCUGGGAGUGGCACCAACCAGGUGCAAGAGGAGA GUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGG CAGCGGCGGCCACGCCGCAGUGGGCAUCGGAGCCG UGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACA AUGGGAGCAGCCUCUAUGACCCUGACAGUGCAGGC CAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGU CCAACCUGCUGAGAGCCCCAGAGCCCCAGCAGCAC CUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCU GCAGGCCAGGGUGCUGGCAGUGGAGCACUAUCUGA GAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGC GGCAAGCUGAUCUGCUGUACCAAUGUGCCCUGGAA CUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCU GGGACAAUAUGACCUGGCUGCAGUGGGAUAAGGAG AUCUCCAACUACACACAGAUCAUCUAUGGCCUGCU GGAAGAAUCUCAGAAUCAGCAGGAAAAGAAUGAAC AGGAUCUGCUGGCACUGGAUGGCGGCGCCGAAAAC CUGUGGGUCACCGUGUACUACGGAGUCCCCGUGUG GAAAGAUGCAGAGACAACCCUGUUCUGCGCUUCCG ACGCUAAAGCUUACGAGACAGAAAAACACAACGUG UGGGCCACUCAUGCCUGCGUGCCUACAGACCCUAA CCCACAGGAAAUCCACCUGGAGAAUGUGACGGAGG AGUUUAACAUGUGGAAGAAUAACAUGGUCGAGCAG AUGCAUGAAGAUAUCAUUUCCUUAUGGGACCAAUC CCUGAAGCCUUGCGUGAAGCUGACCCCACUGUGCG UGACACUGCAAUGCACUAACGUGACCAAUAACAUU ACCGACGAUAUGCGCGGCGAGCUGAAGAACUGCUC UUUCAACAUGACUACCGAGCUGAGAGAUAAGAAAC AGAAAGUGUACAGCCUGUUUUAUCGGUUAGAUGUG GUGCAGAUCAAUGAAAACCAGGGCAAUCGGUCCAA CAAUUCUAACAAGGAAUAUCGCCUGAUCAAUUGUA ACACCUCCGCCAUUACCCAGGCUUGCCCUAAGGUG UCUUUCGAGCCCAUCCCUAUCCACUAUUGCGCCCC AGCUGGAUUUGCUAUCCUGAAGUGUAAGGACAAAA AGUUUAACGGGACCGGACCAUGUCCUAGCGUGUCC ACUGUGCAGUGCACCCAUGGCAUCAAGCCUGUGGU GUCCACCCAACUUCUGCUGAAUGGCUCUCUGGCUG AAGAAGAAGUGAUCAUUAGGUCCGAAAAUAUUACU AAUAACGCUAAAAAUAUCCUGGUCCAGCUGAACAC GCCUGUCCAGAUCAAUUGUACCCGGCCAAAUAACA ACACAGUGAAGUCUAUCAGAAUCGGCCCAGGCCAG GCCUUCUACUACACAGGCGACAUUAUCGGCGAUAU UCGCCAGGCCCACUGUAAUGUGAGCAAAGCUACAU GGAAUGAGACACUGGGCAAGGUAGUCAAACAGCUG AGAAAACAUUUUGGAAACAACACCAUCAUCCGCUU UGCACAGUCUAGCGGCGGCGACCUGGAGGUAACUA CCCACAGCUUCAAUUGUGGCGGCGAGUUCUUUUAC UGUAAUACCAGCGGCCUGUUUAAUAGUACUUGGAU CAGCAACACAUCUGUGCAGGGCUCUAACUCCACUG GCUCUAACGAUAGCAUCACACUGCCUUGUCGGAUC AAGCAAAUCAUCAACAUGUGGCAAAGGAUUGGGCA GGCUAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCC GGUGCGUGAGCAACAUUACAGGCCUGAUCCUGACA AGAGACGGCGGCUCCACCAACUCUACUACCGAGAC AUUCCGGCCCGGCGGCGGCGACAUGCGUGAUAACU GGCGCAGCGAACUGUAUAAAUAUAAAGUGGUGAAG AUCGAGCCUCUGGGCGUGGCCCCAACUAGGUGUAA AAGAAGGGUCGUCGGCUCCCACAGCGGCAGCGGCG GCUCCGGCUCUGGCGGCCACGCGGCUGUCGGCAUC GGCGCCGUGAGCCUGGGCUUUCUGGGCGCCGCCGG CUCCACUAUGGGCGCAGCCUCUAUGACCCUGACUG UCCAGGCUAGAAAUCUGCUGUCUGGAAUCGUGCAG CAGCAGUCUAACCUGCUGAGGGCACCUGAGCCACA ACAGCACCUGCUGAAGGAUACACAUUGGGGCAUCA AGCAGUUACAAGCCAGGGUGCUGGCCGUGGAACAC UACCUGCGCGAUCAGCAAUUACUGGGCAUUUGGGG AUGCUCUGGCAAGCUGAUUUGUUGCACCAAUGUGC CCUGGAACUCCUCUUGGAGCAACAGAAACCUGUCC GAAAUCUGGGAUAACAUGACAUGGCUGCAGUGGGA CAAGGAAAUUUCCAAUUAUACCCAGAUCAUCUAUG GACUGCUGGAAGAAAGUCAGAAUCAGCAGGAGAAG AAUGAACAGGAUCUGCUGGCACUGGAUGGCGGCGC CGAAAACCUGUGGGUCACCGUGUAUUAUGGAGUGC CAGUGUGGAAGGACGCCGAGACCACACUGUUUUGU GCCUCUGAUGCCAAGGCCUACGAGACCGAGAAGCA CAACGUGUGGGCCACCCACGCCUGCGUGCCCACAG ACCCAAAUCCUCAGGAGAUCCACCUGGAGAACGUG ACCGAGGAGUUUAACAUGUGGAAGAACAAUAUGGU GGAGCAGAUGCACGAGGAUAUCAUCUCUCUGUGGG AUCAGUCUCUGAAGCCAUGUGUGAAGCUGACCCCA CUGUGCGUGACCCUGCAGUGUACAAAUGUGACAAA CAACAUCACAGAUGACAUGAGAGGCGAGCUGAAGA ACUGUUCCUUCAAUAUGACCACCGAGCUGAGAGAC AAGAAGCAGAAGGUGUAUUCUCUGUUUUACCGGCU GGACGUGGUGCAGAUCAACGAGAAUCAGGGCAAUC GGUCUAACAACUCCAAUAAGGAGUAUAGACUGAUC AACUGCAACACCUCUGCCAUCACCCAGGCCUGUCC UAAGGUGUCCUUUGAGCCAAUCCCAAUCCACUAUU GCGCCCCUGCCGGCUUUGCCAUCCUGAAGUGCAAG GACAAGAAGUUUAACGGCACAGGCCCCUGCCCAUC CGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGC CUGUGGUGUCCACCCAGCUGCUGCUGAACGGCUCC CUGGCCGAGGAGGAGGUAAUCAUCAGGUCUGAGAA CAUCACAAAUAACGCCAAGAACAUCCUGGUGCAGC UGAACACCCCAGUGCAGAUCAACUGUACCCGGCCU AACAAUAAUACCGUGAAGUCUAUCCGGAUCGGCCC AGGCCAGGCCUUCUACUAUACCGGCGAUAUCAUCG GCGAUAUCAGACAGGCCCACUGCAACGUGUCCAAG GCCACAUGGAACGAGACACUGGGCAAGGUGGUGAA GCAGCUGCGGAAGCACUUUGGCAAUAACACCAUCA UCAGAUUCGCCCAGUCUUCCGGCGGCGACCUGGAG GUGACAACCCACUCCUUCAAUUGCGGCGGCGAGUU CUUUUACUGUAAUACAAGCGGCCUGUUUAAUAGCA CCUGGAUCUCUAACACCUCCGUGCAGGGCUCCAAC AGCACAGGCUCUAAUGAUUCCAUCACCCUGCCUUG CCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGAGAA UCGGCCAGGCCAUGUAUGCCCCUCCAAUCCAGGGC GUGAUCCGCUGCGUGUCCAACAUCACAGGCCUGAU CCUGACAAGAGAUGGCGGCUCCACCAACAGCACCA CAGAGACCUUCAGACCCGGCGGCGGCGACAUGCGC GACAACUGGAGAUCCGAGCUGUAUAAGUACAAGGU GGUGAAGAUCGAGCCCCUGGGCGUGGCCCCAACCC GGUGUAAGCGCAGAGUGGUGGGCAGCCACAGCGGC AGCGGCGGCAGCGGCUCCGGCGGCCACGCCGCCGU GGGCAUCGGCGCCGUGUCCCUGGGCUUCCUGGGCG CCGCCGGCUCCACCAUGGGCGCCGCCUCCAUGACA CUGACAGUGCAGGCCAGAAAUCUGCUGUCCGGCAU CGUGCAGCAGCAGUCCAAUCUGCUGCGGGCCCCUG AGCCACAGCAGCACCUGCUGAAGGAUACCCACUGG GGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCCGU GGAGCACUACCUGAGGGAUCAGCAGCUGCUGGGCA UCUGGGGCUGUUCCGGCAAGCUGAUCUGCUGUACA AACGUGCCCUGGAACAGCUCCUGGUCCAAUAGGAA CCUGUCCGAGAUCUGGGAUAACAUGACCUGGCUGC AGUGGGAUAAGGAGAUCAGCAACUACACACAGAUC AUCUACGGCCUGCUGGAGGAGAGCCAGAAUCAGCA GGAGAAGAACGAGCAGGACCUGCUGGCCCUGGAU BG505_SOSIP_MD39_trimer string 2-RNA (SEQ ID NO: 242) GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUC CGGCGGCUCUGGCAGCGGCGGCCACGCCGCAGUGG GCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCA GCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCU GACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCG UGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAG CCCCAGCAGCACCUGCUGAAGGACACCCACUGGGG CAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGG AGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUC UGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAA UGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACC UGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAG UGGGAUAAGGAGAUCUCCAACUACACACAGAUCAU CUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGG AAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGC GGCAGCGGCAGCGGCGCCGAAAACCUGUGGGUCAC CGUGUACUACGGAGUCCCCGUGUGGAAAGAUGCAG AGACAACCCUGUUCUGCGCUUCCGACGCUAAAGCU UACGAGACAGAAAAACACAACGUGUGGGCCACUCA UGCCUGCGUGCCUACAGACCCUAACCCACAGGAAA UCCACCUGGAGAAUGUGACGGAGGAGUUUAACAUG UGGAAGAAUAACAUGGUCGAGCAGAUGCAUGAAGA UAUCAUUUCCUUAUGGGACCAAUCCCUGAAGCCUU GCGUGAAGCUGACCCCACUGUGCGUGACACUGCAA UGCACUAACGUGACCAAUAACAUUACCGACGAUAU GCGCGGCGAGCUGAAGAACUGCUCUUUCAACAUGA CUACCGAGCUGAGAGAUAAGAAACAGAAAGUGUAC AGCCUGUUUUAUCGGUUAGAUGUGGUGCAGAUCAA UGAAAACCAGGGCAAUCGGUCCAACAAUUCUAACA AGGAAUAUCGCCUGAUCAAUUGUAACACCUCCGCC AUUACCCAGGCUUGCCCUAAGGUGUCUUUCGAGCC CAUCCCUAUCCACUAUUGCGCCCCAGCUGGAUUUG CUAUCCUGAAGUGUAAGGACAAAAAGUUUAACGGG ACCGGACCAUGUCCUAGCGUGUCCACUGUGCAGUG CACCCAUGGCAUCAAGCCUGUGGUGUCCACCCAAC UUCUGCUGAAUGGCUCUCUGGCUGAAGAAGAAGUG AUCAUUAGGUCCGAAAAUAUUACUAAUAACGCUAA AAAUAUCCUGGUCCAGCUGAACACGCCUGUCCAGA UCAAUUGUACCCGGCCAAAUAACAACACAGUGAAG UCUAUCAGAAUCGGCCCAGGCCAGGCCUUCUACUA CACAGGCGACAUUAUCGGCGAUAUUCGCCAGGCCC ACUGUAAUGUGAGCAAAGCUACAUGGAAUGAGACA CUGGGCAAGGUAGUCAAACAGCUGAGAAAACAUUU UGGAAACAACACCAUCAUCCGCUUUGCACAGUCUA GCGGCGGCGACCUGGAGGUAACUACCCACAGCUUC AAUUGUGGCGGCGAGUUCUUUUACUGUAAUACCAG CGGCCUGUUUAAUAGUACUUGGAUCAGCAACACAU CUGUGCAGGGCUCUAACUCCACUGGCUCUAACGAU AGCAUCACACUGCCUUGUCGGAUCAAGCAAAUCAU CAACAUGUGGCAAAGGAUUGGGCAGGCUAUGUAUG CCCCUCCAAUCCAGGGCGUGAUCCGGUGCGUGAGC AACAUUACAGGCCUGAUCCUGACAAGAGACGGCGG CUCCACCAACUCUACUACCGAGACAUUCCGGCCCG GCGGCGGCGACAUGCGUGAUAACUGGCGCAGCGAA CUGUAUAAAUAUAAAGUGGUGAAGAUCGAGCCUCU GGGCGUGGCCCCAACUAGGUGUAAAAGAAGGGUCG UCGGCUCCCACAGCGGCAGCGGCGGCUCCGGCUCU GGCGGCCACGCGGCUGUCGGCAUCGGCGCCGUGAG CCUGGGCUUUCUGGGCGCCGCCGGCUCCACUAUGG GCGCAGCCUCUAUGACCCUGACUGUCCAGGCUAGA AAUCUGCUGUCUGGAAUCGUGCAGCAGCAGUCUAA CCUGCUGAGGGCACCUGAGCCACAACAGCACCUGC UGAAGGAUACACAUUGGGGCAUCAAGCAGUUACAA GCCAGGGUGCUGGCCGUGGAACACUACCUGCGCGA UCAGCAAUUACUGGGCAUUUGGGGAUGCUCUGGCA AGCUGAUUUGUUGCACCAAUGUGCCCUGGAACUCC UCUUGGAGCAACAGAAACCUGUCCGAAAUCUGGGA UAACAUGACAUGGCUGCAGUGGGACAAGGAAAUUU CCAAUUAUACCCAGAUCAUCUAUGGACUGCUGGAA GAAAGUCAGAAUCAGCAGGAGAAGAAUGAACAGGA UCUGCUGGCACUGGAUGGCGGCAGCGGCAGCGGCG CCGAAAACCUGUGGGUCACCGUGUAUUAUGGAGUG CCAGUGUGGAAGGACGCCGAGACCACACUGUUUUG UGCCUCUGAUGCCAAGGCCUACGAGACCGAGAAGC ACAACGUGUGGGCCACCCACGCCUGCGUGCCCACA GACCCAAAUCCUCAGGAGAUCCACCUGGAGAACGU GACCGAGGAGUUUAACAUGUGGAAGAACAAUAUGG UGGAGCAGAUGCACGAGGAUAUCAUCUCUCUGUGG GAUCAGUCUCUGAAGCCAUGUGUGAAGCUGACCCC ACUGUGCGUGACCCUGCAGUGUACAAAUGUGACAA ACAACAUCACAGAUGACAUGAGAGGCGAGCUGAAG AACUGUUCCUUCAAUAUGACCACCGAGCUGAGAGA CAAGAAGCAGAAGGUGUAUUCUCUGUUUUACCGGC UGGACGUGGUGCAGAUCAACGAGAAUCAGGGCAAU CGGUCUAACAACUCCAAUAAGGAGUAUAGACUGAU CAACUGCAACACCUCUGCCAUCACCCAGGCCUGUC CUAAGGUGUCCUUUGAGCCAAUCCCAAUCCACUAU UGCGCCCCUGCCGGCUUUGCCAUCCUGAAGUGCAA GGACAAGAAGUUUAACGGCACAGGCCCCUGCCCAU CCGUGAGCACAGUGCAGUGUACCCACGGCAUCAAG CCUGUGGUGUCCACCCAGCUGCUGCUGAACGGCUC CCUGGCCGAGGAGGAGGUAAUCAUCAGGUCUGAGA ACAUCACAAAUAACGCCAAGAACAUCCUGGUGCAG CUGAACACCCCAGUGCAGAUCAACUGUACCCGGCC UAACAAUAAUACCGUGAAGUCUAUCCGGAUCGGCC CAGGCCAGGCCUUCUACUAUACCGGCGAUAUCAUC GGCGAUAUCAGACAGGCCCACUGCAACGUGUCCAA GGCCACAUGGAACGAGACACUGGGCAAGGUGGUGA AGCAGCUGCGGAAGCACUUUGGCAAUAACACCAUC AUCAGAUUCGCCCAGUCUUCCGGCGGCGACCUGGA GGUGACAACCCACUCCUUCAAUUGCGGCGGCGAGU UCUUUUACUGUAAUACAAGCGGCCUGUUUAAUAGC ACCUGGAUCUCUAACACCUCCGUGCAGGGCUCCAA CAGCACAGGCUCUAAUGAUUCCAUCACCCUGCCUU GCCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGAGA AUCGGCCAGGCCAUGUAUGCCCCUCCAAUCCAGGG CGUGAUCCGCUGCGUGUCCAACAUCACAGGCCUGA UCCUGACAAGAGAUGGCGGCUCCACCAACAGCACC ACAGAGACCUUCAGACCCGGCGGCGGCGACAUGCG CGACAACUGGAGAUCCGAGCUGUAUAAGUACAAGG UGGUGAAGAUCGAGCCCCUGGGCGUGGCCCCAACC CGGUGUAAGCGCAGAGUGGUGGGCAGCCACAGCGG CAGCGGCGGCAGCGGCUCCGGCGGCCACGCCGCCG UGGGCAUCGGCGCCGUGUCCCUGGGCUUCCUGGGC GCCGCCGGCUCCACCAUGGGCGCCGCCUCCAUGAC ACUGACAGUGCAGGCCAGAAAUCUGCUGUCCGGCA UCGUGCAGCAGCAGUCCAAUCUGCUGCGGGCCCCU GAGCCACAGCAGCACCUGCUGAAGGAUACCCACUG GGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCCG UGGAGCACUACCUGAGGGAUCAGCAGCUGCUGGGC AUCUGGGGCUGUUCCGGCAAGCUGAUCUGCUGUAC AAACGUGCCCUGGAACAGCUCCUGGUCCAAUAGGA ACCUGUCCGAGAUCUGGGAUAACAUGACCUGGCUG CAGUGGGAUAAGGAGAUCAGCAACUACACACAGAU CAUCUACGGCCUGCUGGAGGAGAGCCAGAAUCAGC AGGAGAAGAACGAGCAGGACCUGCUGGCCCUGGAU UGAUAACUCGAG (22) BG505_MD39_link14_gp140-PDGFR (SEQ ID NO: 243) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGC CGCUACAAGAGUGCAUUCCGCCGAAAACCUGUGGG UCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGAC GCCGAGACUACGCUGUUCUGCGCCAGCGAUGCCAA GGCCUACGAGACAGAGAAGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCUACAGACCCAAACCCCCAG GAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAG CCCUGCGUGAAGCUGACCCCUCUGUGCGUGACACU GCAGUGUACCAACGUGACAAACAAUAUCACCGACG AUAUGCGGGGCGAGCUGAAGAAUUGUAGCUUCAAC AUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGU GUACUCCCUGUUUUAUAGACUGGAUGUGGUGCAGA UCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGC AACAAGGAGUACCGCCUGAUCAAUUGCAACACCUC CGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCG AGCCUAUCCCAAUCCACUAUUGCGCCCCAGCCGGC UUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAA CGGAACCGGACCAUGCCCUUCCGUGUCUACCGUGC AGUGUACACACGGCAUCAAGCCUGUGGUGUCUACA CAGCUGCUGCUGAAUGGCAGCCUGGCCGAGGAGGA AGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUG CCAAGAAUAUCCUGGUGCAGCUGAACACACCAGUG CAGAUCAAUUGCACCCGGCCCAACAAUAACACAGU GAAGUCUAUCCGCAUCGGCCCAGGCCAGGCCUUUU ACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAG GCCCACUGUAAUGUGAGCAAGGCCACCUGGAACGA GACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGC ACUUCGGCAAUAACACCAUCAUCAGAUUUGCACAG AGCUCCGGCGGCGACCUGGAGGUGACCACACACUC CUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAACA CAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAAC ACAUCUGUGCAGGGCAGCAAUUCCACCGGCAGCAA CGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGA UCAUCAACAUGUGGCAGCGCAUCGGCCAGGCCAUG UAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGU GAGCAAUAUCACCGGCCUGAUCCUGACACGCGACG GCGGCUCUACCAACAGCACCACAGAGACAUUCCGG CCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUC UGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGC CUCUGGGAGUGGCACCAACCAGGUGCAAGAGGAGA GUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGG CAGCGGCGGCCACGCCGCAGUGGGCAUCGGAGCCG UGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACA AUGGGAGCAGCCUCUAUGACCCUGACAGUGCAGGC CAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGU CCAACCUGCUGAGAGCCCCAGAGCCCCAGCAGCAC CUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCU GCAGGCCAGGGUGCUGGCAGUGGAGCACUAUCUGA GAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGC GGCAAGCUGAUCUGCUGUACCAAUGUGCCCUGGAA CUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCU GGGACAAUAUGACCUGGCUGCAGUGGGAUAAGGAG AUCUCCAACUACACACAGAUCAUCUAUGGCCUGCU GGAAGAAUCUCAGAAUCAGCAGGAAAAGAAUGAAC AGGAUCUGCUGGCACUGGAUGGAGGAGGAAGCGGG GGAAGCGGGGGAAGCGGAGGAAGCGGGGGAAGCGG GGGAAGCAACGCCGUGGGCCAGGACACCCAGGAAG UGAUCGUGGUGCCCCACAGCCUGCCUUUCAAGGUG GUGGUCAUCUCCGCCAUCCUGGCCCUGGUCGUGCU GACUAUUAUUUCCCUGAUUAUCCUGAUUAUGCUGU GGCAGAAGAAGCCCAGA BG505_MD39_gp140_foldon-PDGFR (SEQ ID NO: 244) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGC CGCUACAAGAGUGCAUUCCGCCGAAAACCUGUGGG UCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGAC GCCGAGACUACGCUGUUCUGCGCCAGCGAUGCCAA GGCCUACGAGACAGAGAAGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCUACAGACCCAAACCCCCAG GAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAG CCCUGCGUGAAGCUGACCCCUCUGUGCGUGACACU GCAGUGUACCAACGUGACAAACAAUAUCACCGACG AUAUGCGGGGCGAGCUGAAGAAUUGUAGCUUCAAC AUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGU GUACUCCCUGUUUUAUAGACUGGAUGUGGUGCAGA UCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGC AACAAGGAGUACCGCCUGAUCAAUUGCAACACCUC CGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCG AGCCUAUCCCAAUCCACUAUUGCGCCCCAGCCGGC UUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAA CGGAACCGGACCAUGCCCUUCCGUGUCUACCGUGC AGUGUACACACGGCAUCAAGCCUGUGGUGUCUACA CAGCUGCUGCUGAAUGGCAGCCUGGCCGAGGAGGA AGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUG CCAAGAAUAUCCUGGUGCAGCUGAACACACCAGUG CAGAUCAAUUGCACCCGGCCCAACAAUAACACAGU GAAGUCUAUCCGCAUCGGCCCAGGCCAGGCCUUUU ACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAG GCCCACUGUAAUGUGAGCAAGGCCACCUGGAACGA GACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGC ACUUCGGCAAUAACACCAUCAUCAGAUUUGCACAG AGCUCCGGCGGCGACCUGGAGGUGACCACACACUC CUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAACA CAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAAC ACAUCUGUGCAGGGCAGCAAUUCCACCGGCAGCAA CGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGA UCAUCAACAUGUGGCAGCGCAUCGGCCAGGCCAUG UAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGU GAGCAAUAUCACCGGCCUGAUCCUGACACGCGACG GCGGCUCUACCAACAGCACCACAGAGACAUUCCGG CCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUC UGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGC CUCUGGGAGUGGCACCAACCAGGUGCAAGAGGAGA GUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGG CAGCGGCGGCCACGCCGCAGUGGGCAUCGGAGCCG UGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACA AUGGGAGCAGCCUCUAUGACCCUGACAGUGCAGGC CAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGU CCAACCUGCUGAGAGCCCCAGAGCCCCAGCAGCAC CUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCU GCAGGCCAGGGUGCUGGCAGUGGAGCACUAUCUGA GAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGC GGCAAGCUGAUCUGCUGUACCAAUGUGCCCUGGAA CUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCU GGGACAAUAUGACCUGGCUGCAGUGGGAUAAGGAG AUCUCCAACUACACACAGAUCAUCUAUGGCCUGCU GGAAGAAUCUCAGAAUCAGCAGGAAAAGAAUGAAC AGGAUCUGCUGGCACUGGAUGGAGGAGGAAGCGGG GGAAGCGGCGGCGGCUACAUCCCUGAGGCCCCAAG GGACGGACAGGCCUAUGUGAGAAAGGAUGGCGAGU GGGUGCUGCUGUCCACCUUCCUGGGGGGAAGCGGA GGAAGCGGGGGAAGCGGGGGAAGCAACGCCGUGGG CCAGGACACCCAGGAAGUGAUCGUGGUGCCCCACA GCCUGCCUUUCAAGGUGGUGGUCAUCUCCGCCAUC CUGGCCCUGGUCGUGCUGACUAUUAUUUCCCUGAU UAUCCUGAUUAUGCUGUGGCAGAAGAAGCCCAGA BG505_MD39_TS1_gp140-PDGFR (SEQ ID NO: 245) GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUC CGGCGGCUCUGGCAGCGGCGGCCACGCCGCAGUGG GCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCA GCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCU GACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCG UGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAG CCCCAGCAGCACCUGCUGAAGGACACCCACUGGGG CAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGG AGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUC UGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAA UGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACC UGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAG UGGGAUAAGGAGAUCUCCAACUACACACAGAUCAU CUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGG AAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGC GGCGCCGAAAACCUGUGGGUCACCGUGUACUACGG AGUCCCCGUGUGGAAAGAUGCAGAGACAACCCUGU UCUGCGCUUCCGACGCUAAAGCUUACGAGACAGAA AAACACAACGUGUGGGCCACUCAUGCCUGCGUGCC UACAGACCCUAACCCACAGGAAAUCCACCUGGAGA AUGUGACGGAGGAGUUUAACAUGUGGAAGAAUAAC AUGGUCGAGCAGAUGCAUGAAGAUAUCAUUUCCUU AUGGGACCAAUCCCUGAAGCCUUGCGUGAAGCUGA CCCCACUGUGCGUGACACUGCAAUGCACUAACGUG ACCAAUAACAUUACCGACGAUAUGCGCGGCGAGCU GAAGAACUGCUCUUUCAACAUGACUACCGAGCUGA GAGAUAAGAAACAGAAAGUGUACAGCCUGUUUUAU CGGUUAGAUGUGGUGCAGAUCAAUGAAAACCAGGG CAAUCGGUCCAACAAUUCUAACAAGGAAUAUCGCC UGAUCAAUUGUAACACCUCCGCCAUUACCCAGGCU UGCCCUAAGGUGUCUUUCGAGCCCAUCCCUAUCCA CUAUUGCGCCCCAGCUGGAUUUGCUAUCCUGAAGU GUAAGGACAAAAAGUUUAACGGGACCGGACCAUGU CCUAGCGUGUCCACUGUGCAGUGCACCCAUGGCAU CAAGCCUGUGGUGUCCACCCAACUUCUGCUGAAUG GCUCUCUGGCUGAAGAAGAAGUGAUCAUUAGGUCC GAAAAUAUUACUAAUAACGCUAAAAAUAUCCUGGU CCAGCUGAACACGCCUGUCCAGAUCAAUUGUACCC GGCCAAAUAACAACACAGUGAAGUCUAUCAGAAUC GGCCCAGGCCAGGCCUUCUACUACACAGGCGACAU UAUCGGCGAUAUUCGCCAGGCCCACUGUAAUGUGA GCAAAGCUACAUGGAAUGAGACACUGGGCAAGGUA GUCAAACAGCUGAGAAAACAUUUUGGAAACAACAC CAUCAUCCGCUUUGCACAGUCUAGCGGCGGCGACC UGGAGGUAACUACCCACAGCUUCAAUUGUGGCGGC GAGUUCUUUUACUGUAAUACCAGCGGCCUGUUUAA UAGUACUUGGAUCAGCAACACAUCUGUGCAGGGCU CUAACUCCACUGGCUCUAACGAUAGCAUCACACUG CCUUGUCGGAUCAAGCAAAUCAUCAACAUGUGGCA AAGGAUUGGGCAGGCUAUGUAUGCCCCUCCAAUCC AGGGCGUGAUCCGGUGCGUGAGCAACAUUACAGGC CUGAUCCUGACAAGAGACGGCGGCUCCACCAACUC UACUACCGAGACAUUCCGGCCCGGCGGCGGCGACA UGCGUGAUAACUGGCGCAGCGAACUGUAUAAAUAU AAAGUGGUGAAGAUCGAGCCUCUGGGCGUGGCCCC AACUAGGUGUAAAAGAAGGGUCGUCGGCUCCCACA GCGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCG GCUGUCGGCAUCGGCGCCGUGAGCCUGGGCUUUCU GGGCGCCGCCGGCUCCACUAUGGGCGCAGCCUCUA UGACCCUGACUGUCCAGGCUAGAAAUCUGCUGUCU GGAAUCGUGCAGCAGCAGUCUAACCUGCUGAGGGC ACCUGAGCCACAACAGCACCUGCUGAAGGAUACAC AUUGGGGCAUCAAGCAGUUACAAGCCAGGGUGCUG GCCGUGGAACACUACCUGCGCGAUCAGCAAUUACU GGGCAUUUGGGGAUGCUCUGGCAAGCUGAUUUGUU GCACCAAUGUGCCCUGGAACUCCUCUUGGAGCAAC AGAAACCUGUCCGAAAUCUGGGAUAACAUGACAUG GCUGCAGUGGGACAAGGAAAUUUCCAAUUAUACCC AGAUCAUCUAUGGACUGCUGGAAGAAAGUCAGAAU CAGCAGGAGAAGAAUGAACAGGAUCUGCUGGCACU GGAUGGCGGCGCCGAAAACCUGUGGGUCACCGUGU AUUAUGGAGUGCCAGUGUGGAAGGACGCCGAGACC ACACUGUUUUGUGCCUCUGAUGCCAAGGCCUACGA GACCGAGAAGCACAACGUGUGGGCCACCCACGCCU GCGUGCCCACAGACCCAAAUCCUCAGGAGAUCCAC CUGGAGAACGUGACCGAGGAGUUUAACAUGUGGAA GAACAAUAUGGUGGAGCAGAUGCACGAGGAUAUCA UCUCUCUGUGGGAUCAGUCUCUGAAGCCAUGUGUG AAGCUGACCCCACUGUGCGUGACCCUGCAGUGUAC AAAUGUGACAAACAACAUCACAGAUGACAUGAGAG GCGAGCUGAAGAACUGUUCCUUCAAUAUGACCACC GAGCUGAGAGACAAGAAGCAGAAGGUGUAUUCUCU GUUUUACCGGCUGGACGUGGUGCAGAUCAACGAGA AUCAGGGCAAUCGGUCUAACAACUCCAAUAAGGAG UAUAGACUGAUCAACUGCAACACCUCUGCCAUCAC CCAGGCCUGUCCUAAGGUGUCCUUUGAGCCAAUCC CAAUCCACUAUUGCGCCCCUGCCGGCUUUGCCAUC CUGAAGUGCAAGGACAAGAAGUUUAACGGCACAGG CCCCUGCCCAUCCGUGAGCACAGUGCAGUGUACCC ACGGCAUCAAGCCUGUGGUGUCCACCCAGCUGCUG CUGAACGGCUCCCUGGCCGAGGAGGAGGUAAUCAU CAGGUCUGAGAACAUCACAAAUAACGCCAAGAACA UCCUGGUGCAGCUGAACACCCCAGUGCAGAUCAAC UGUACCCGGCCUAACAAUAAUACCGUGAAGUCUAU CCGGAUCGGCCCAGGCCAGGCCUUCUACUAUACCG GCGAUAUCAUCGGCGAUAUCAGACAGGCCCACUGC AACGUGUCCAAGGCCACAUGGAACGAGACACUGGG CAAGGUGGUGAAGCAGCUGCGGAAGCACUUUGGCA AUAACACCAUCAUCAGAUUCGCCCAGUCUUCCGGC GGCGACCUGGAGGUGACAACCCACUCCUUCAAUUG CGGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCC UGUUUAAUAGCACCUGGAUCUCUAACACCUCCGUG CAGGGCUCCAACAGCACAGGCUCUAAUGAUUCCAU CACCCUGCCUUGCCGGAUCAAGCAGAUCAUCAAUA UGUGGCAGAGAAUCGGCCAGGCCAUGUAUGCCCCU CCAAUCCAGGGCGUGAUCCGCUGCGUGUCCAACAU CACAGGCCUGAUCCUGACAAGAGAUGGCGGCUCCA CCAACAGCACCACAGAGACCUUCAGACCCGGCGGC GGCGACAUGCGCGACAACUGGAGAUCCGAGCUGUA UAAGUACAAGGUGGUGAAGAUCGAGCCCCUGGGCG UGGCCCCAACCCGGUGUAAGCGCAGAGUGGUGGGC AGCCACAGCGGCAGCGGCGGCAGCGGCUCCGGCGG CCACGCCGCCGUGGGCAUCGGCGCCGUGUCCCUGG GCUUCCUGGGCGCCGCCGGCUCCACCAUGGGCGCC GCCUCCAUGACACUGACAGUGCAGGCCAGAAAUCU GCUGUCCGGCAUCGUGCAGCAGCAGUCCAAUCUGC UGCGGGCCCCUGAGCCACAGCAGCACCUGCUGAAG GAUACCCACUGGGGCAUCAAGCAGCUGCAGGCCCG GGUGCUGGCCGUGGAGCACUACCUGAGGGAUCAGC AGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGCUG AUCUGCUGUACAAACGUGCCCUGGAACAGCUCCUG GUCCAAUAGGAACCUGUCCGAGAUCUGGGAUAACA UGACCUGGCUGCAGUGGGAUAAGGAGAUCAGCAAC UACACACAGAUCAUCUACGGCCUGCUGGAGGAGAG CCAGAAUCAGCAGGAGAAGAACGAGCAGGACCUGC UGGCCCUGGAUGGAGGAGGAAGCGGGGGAAGCGGG GGAAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAA CGCCGUGGGCCAGGACACCCAGGAAGUGAUCGUGG UGCCCCACAGCCUGCCUUUCAAGGUGGUGGUCAUC UCCGCCAUCCUGGCCCUGGUCGUGCUGACUAUUAU UUCCCUGAUUAUCCUGAUUAUGCUGUGGCAGAAGA AGCCCAGA BG505_MD39_TS1_gp140-PDGFR (SEQ ID NO: 246) GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUC CGGCGGCUCUGGCAGCGGCGGCCACGCCGCAGUGG GCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCA GCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCU GACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCG UGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAG CCCCAGCAGCACCUGCUGAAGGACACCCACUGGGG CAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGG AGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUC UGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAA UGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACC UGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAG UGGGAUAAGGAGAUCUCCAACUACACACAGAUCAU CUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGG AAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGC GGCGCCGAAAACCUGUGGGUCACCGUGUACUACGG AGUCCCCGUGUGGAAAGAUGCAGAGACAACCCUGU UCUGCGCUUCCGACGCUAAAGCUUACGAGACAGAA AAACACAACGUGUGGGCCACUCAUGCCUGCGUGCC UACAGACCCUAACCCACAGGAAAUCCACCUGGAGA AUGUGACGGAGGAGUUUAACAUGUGGAAGAAUAAC AUGGUCGAGCAGAUGCAUGAAGAUAUCAUUUCCUU AUGGGACCAAUCCCUGAAGCCUUGCGUGAAGCUGA CCCCACUGUGCGUGACACUGCAAUGCACUAACGUG ACCAAUAACAUUACCGACGAUAUGCGCGGCGAGCU GAAGAACUGCUCUUUCAACAUGACUACCGAGCUGA GAGAUAAGAAACAGAAAGUGUACAGCCUGUUUUAU CGGUUAGAUGUGGUGCAGAUCAAUGAAAACCAGGG CAAUCGGUCCAACAAUUCUAACAAGGAAUAUCGCC UGAUCAAUUGUAACACCUCCGCCAUUACCCAGGCU UGCCCUAAGGUGUCUUUCGAGCCCAUCCCUAUCCA CUAUUGCGCCCCAGCUGGAUUUGCUAUCCUGAAGU GUAAGGACAAAAAGUUUAACGGGACCGGACCAUGU CCUAGCGUGUCCACUGUGCAGUGCACCCAUGGCAU CAAGCCUGUGGUGUCCACCCAACUUCUGCUGAAUG GCUCUCUGGCUGAAGAAGAAGUGAUCAUUAGGUCC GAAAAUAUUACUAAUAACGCUAAAAAUAUCCUGGU CCAGCUGAACACGCCUGUCCAGAUCAAUUGUACCC GGCCAAAUAACAACACAGUGAAGUCUAUCAGAAUC GGCCCAGGCCAGGCCUUCUACUACACAGGCGACAU UAUCGGCGAUAUUCGCCAGGCCCACUGUAAUGUGA GCAAAGCUACAUGGAAUGAGACACUGGGCAAGGUA GUCAAACAGCUGAGAAAACAUUUUGGAAACAACAC CAUCAUCCGCUUUGCACAGUCUAGCGGCGGCGACC UGGAGGUAACUACCCACAGCUUCAAUUGUGGCGGC GAGUUCUUUUACUGUAAUACCAGCGGCCUGUUUAA UAGUACUUGGAUCAGCAACACAUCUGUGCAGGGCU CUAACUCCACUGGCUCUAACGAUAGCAUCACACUG CCUUGUCGGAUCAAGCAAAUCAUCAACAUGUGGCA AAGGAUUGGGCAGGCUAUGUAUGCCCCUCCAAUCC AGGGCGUGAUCCGGUGCGUGAGCAACAUUACAGGC CUGAUCCUGACAAGAGACGGCGGCUCCACCAACUC UACUACCGAGACAUUCCGGCCCGGCGGCGGCGACA UGCGUGAUAACUGGCGCAGCGAACUGUAUAAAUAU AAAGUGGUGAAGAUCGAGCCUCUGGGCGUGGCCCC AACUAGGUGUAAAAGAAGGGUCGUCGGCUCCCACA GCGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCG GCUGUCGGCAUCGGCGCCGUGAGCCUGGGCUUUCU GGGCGCCGCCGGCUCCACUAUGGGCGCAGCCUCUA UGACCCUGACUGUCCAGGCUAGAAAUCUGCUGUCU GGAAUCGUGCAGCAGCAGUCUAACCUGCUGAGGGC ACCUGAGCCACAACAGCACCUGCUGAAGGAUACAC AUUGGGGCAUCAAGCAGUUACAAGCCAGGGUGCUG GCCGUGGAACACUACCUGCGCGAUCAGCAAUUACU GGGCAUUUGGGGAUGCUCUGGCAAGCUGAUUUGUU GCACCAAUGUGCCCUGGAACUCCUCUUGGAGCAAC AGAAACCUGUCCGAAAUCUGGGAUAACAUGACAUG GCUGCAGUGGGACAAGGAAAUUUCCAAUUAUACCC AGAUCAUCUAUGGACUGCUGGAAGAAAGUCAGAAU CAGCAGGAGAAGAAUGAACAGGAUCUGCUGGCACU GGAUGGCGGCGCCGAAAACCUGUGGGUCACCGUGU AUUAUGGAGUGCCAGUGUGGAAGGACGCCGAGACC ACACUGUUUUGUGCCUCUGAUGCCAAGGCCUACGA GACCGAGAAGCACAACGUGUGGGCCACCCACGCCU GCGUGCCCACAGACCCAAAUCCUCAGGAGAUCCAC CUGGAGAACGUGACCGAGGAGUUUAACAUGUGGAA GAACAAUAUGGUGGAGCAGAUGCACGAGGAUAUCA UCUCUCUGUGGGAUCAGUCUCUGAAGCCAUGUGUG AAGCUGACCCCACUGUGCGUGACCCUGCAGUGUAC AAAUGUGACAAACAACAUCACAGAUGACAUGAGAG GCGAGCUGAAGAACUGUUCCUUCAAUAUGACCACC GAGCUGAGAGACAAGAAGCAGAAGGUGUAUUCUCU GUUUUACCGGCUGGACGUGGUGCAGAUCAACGAGA AUCAGGGCAAUCGGUCUAACAACUCCAAUAAGGAG UAUAGACUGAUCAACUGCAACACCUCUGCCAUCAC CCAGGCCUGUCCUAAGGUGUCCUUUGAGCCAAUCC CAAUCCACUAUUGCGCCCCUGCCGGCUUUGCCAUC CUGAAGUGCAAGGACAAGAAGUUUAACGGCACAGG CCCCUGCCCAUCCGUGAGCACAGUGCAGUGUACCC ACGGCAUCAAGCCUGUGGUGUCCACCCAGCUGCUG CUGAACGGCUCCCUGGCCGAGGAGGAGGUAAUCAU CAGGUCUGAGAACAUCACAAAUAACGCCAAGAACA UCCUGGUGCAGCUGAACACCCCAGUGCAGAUCAAC UGUACCCGGCCUAACAAUAAUACCGUGAAGUCUAU CCGGAUCGGCCCAGGCCAGGCCUUCUACUAUACCG GCGAUAUCAUCGGCGAUAUCAGACAGGCCCACUGC AACGUGUCCAAGGCCACAUGGAACGAGACACUGGG CAAGGUGGUGAAGCAGCUGCGGAAGCACUUUGGCA AUAACACCAUCAUCAGAUUCGCCCAGUCUUCCGGC GGCGACCUGGAGGUGACAACCCACUCCUUCAAUUG CGGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCC UGUUUAAUAGCACCUGGAUCUCUAACACCUCCGUG CAGGGCUCCAACAGCACAGGCUCUAAUGAUUCCAU CACCCUGCCUUGCCGGAUCAAGCAGAUCAUCAAUA UGUGGCAGAGAAUCGGCCAGGCCAUGUAUGCCCCU CCAAUCCAGGGCGUGAUCCGCUGCGUGUCCAACAU CACAGGCCUGAUCCUGACAAGAGAUGGCGGCUCCA CCAACAGCACCACAGAGACCUUCAGACCCGGCGGC GGCGACAUGCGCGACAACUGGAGAUCCGAGCUGUA UAAGUACAAGGUGGUGAAGAUCGAGCCCCUGGGCG UGGCCCCAACCCGGUGUAAGCGCAGAGUGGUGGGC AGCCACAGCGGCAGCGGCGGCAGCGGCUCCGGCGG CCACGCCGCCGUGGGCAUCGGCGCCGUGUCCCUGG GCUUCCUGGGCGCCGCCGGCUCCACCAUGGGCGCC GCCUCCAUGACACUGACAGUGCAGGCCAGAAAUCU GCUGUCCGGCAUCGUGCAGCAGCAGUCCAAUCUGC UGCGGGCCCCUGAGCCACAGCAGCACCUGCUGAAG GAUACCCACUGGGGCAUCAAGCAGCUGCAGGCCCG GGUGCUGGCCGUGGAGCACUACCUGAGGGAUCAGC AGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGCUG AUCUGCUGUACAAACGUGCCCUGGAACAGCUCCUG GUCCAAUAGGAACCUGUCCGAGAUCUGGGAUAACA UGACCUGGCUGCAGUGGGAUAAGGAGAUCAGCAAC UACACACAGAUCAUCUACGGCCUGCUGGAGGAGAG CCAGAAUCAGCAGGAGAAGAACGAGCAGGACCUGC UGGCCCUGGAUGGAGGAGGAAGCGGGGGAAGCGGG GGAAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAA CGCCGUGGGCCAGGACACCCAGGAAGUGAUCGUGG UGCCCCACAGCCUGCCUUUCAAGGUGGUGGUCAUC UCCGCCAUCCUGGCCCUGGUCGUGCUGACUAUUAU UUCCCUGAUUAUCCUGAUUAUGCUGUGGCAGAAGA AGCCCAGA TRO11_AY835445_MD39_L14G8-RNA (SEQ ID NO: 247) AUGGAUUGGACUUGGAUUCUGUUUCUGGUCGCUGC UGCUACUCGGGUGCAUUCUCAGGGCCAGCUGUGGG UCACUGUCUACUACGGCGUGCCAGUGUGGAAGGAC GCCUCUACCACACUGUUUUGCGCCAGCGACGCCAA GGCCUACGAUACAGAGGUGCACAACGUGUGGGCAA CACACGCAUGCGUGCCAACCGAUCCAAAUCCCCAG GAGGUGGUGCUGGGCAACGUGACCGAGAACUUCAA UAUGUGGAAGAACAAUAUGGUGGACCAGAUGCACG AGGAUAUCAUCUCUCUGUGGGACCAGAGCCUGAAG CCCUGCGUGAAGCUGACCCCUCUGUGCGUGACACU GAAUUGUACCGAUAACAUCACCAACACAAAUACCA ACAGCUCCAAGAACUCUAGCACACACUCCUAUAAC AAUUCUCUGGAGGGCGAGAUGAAGAAUUGUUCCUU UAACAUCACCGCCGGCAUCCGGGACAAGGUGAAGA AGGAGUACGCCCUGUUCUAUAAGCUGGAUGUGGUG CCCAUCGAGGAGGACAAGGAUACAAAUAAGACCAC AUACCGGCUGCGCAGCUGCAACACAUCCGUGAUCA CCCAGGCCUGUCCUAAGGUGACCUUUGAGCCUAUC CCAAUCCACUAUUGCGCCCCAGCCGGCUUCGCCAU CCUGAAGUGUAAUGACAAGAAGUUUAACGGCACAG GCCCCUGCACCAACGUGUCUACAGUGCAGUGUACC CACGGCAUCAGGCCUGUGGUGUCCACCCAGCUGCU GCUGAAUGGCUCUCUGGCCGAGGAGGAAGUGAUCA UCAGAAGCGAGAACUUUACAAACAAUGCCAAGACC AUCAUCGUGCAGCUGAAUGAGUCUAUCGCCAUCAA CUGCACAAGGCCAAACAAUAACACCGUGAGAAGCA UCCACAUCGGACCAGGAAGGGCCUUCUACUAUACC GGCGACAUCAUCGGCGAUAUCAGGCAGGCCCACUG UAAUAUCUCCAGAACAGAGUGGAACUCUACCCUGC GGCAGAUCGUGACAAAGCUGCGCGAGCAGCUGGGC GACCCUAACAAGACCAUCAUCUUCGCCCAGUCCUC UGGCGGCGAUACAGAGAUCACCAUGCACUCCUUUA AUUGCGGCGGCGAGUUCUUUUACUGUAACACCACA AAGCUGUUCAAUUCUACCUGGAACGGCAAUAACAC CACAGAGUCCGACUCUACAGGCGAGAAUAUCACCC UGCCAUGCCGGAUCAAGCAGAUCAUCAACCUGUGG CAGGAAGUGGGCAAGGCCAUGUAUGCCCCUCCCAU CAAGGGCCAGAUCUCCUGUAGCUCCAACAUCACAG GCCUGCUGCUGACCCGCGACGGCGGAAAUAACAAU UCUAGCGGACCAGAGACAUUCAGGCCUGGCGGCGG CAAUAUGAAGGAUAACUGGAGAAGCGAGCUGUACA AGUAUAAAGUGAUCAAGAUCGAGCCUCUGGGAGUG GCACCAACCAGGUGCAAGAGGAGAGUGGUGGGCAG CCACUCCGGCUCUGGCGGCAGCGGCUCCGGCGGCC ACGCAGCAGUGGGCACACUGGGCGCCAUGAGCCUG GGCUUCCUGGGAGCAGCAGGCAGCACCAUGGGAGC AGCAUCCGUGACACUGACCGUGCAGGCAAGGCUGC UGCUGUCCGGCAUCGUGCAGCAGCAGAACAAUCUG CUGAGGGCACCAGAGCCUCAGCAGCACAUGCUGCA GGACACACACUGGGGCAUCAAGCAGCUGCAGGCCC GGGUGCUGGCAGUGGAGCACUACCUGCGCGAUCAG CAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCU GAUCUGCUGUACCAAUGUGCCUUGGAACGCCUCUU GGAGCAAUAAGAGCCUGAACAAUAUCUGGGAGAAU AUGACAUGGAUGAACUGGUCCAGAGAGAUCGACAA CUACACCGAUCUGAUCUAUAUCCUGCUGGAGAAGU CACAGAUUCAGCAGGAGAAGAACAAUCAGAGCCUG CUGGAACUGGAU X2278_FJ817366_MD39_L14G8-RNA (SEQ ID NO: 248) AUGGACUGGACCUGGAUUCUGUUCCUGGUCGCCGC UGCUACAAGAGUGCAUUCUACAAAUAACCUGUGGG UGACUGUCUACUAUGGAGUGCCCGUGUGGAAGGAG GCCACCACAACCCUGUUCUGCGCCAGCGAGGCCAA GGCCUACGACACAGAGGUGCACAACAUCUGGGCCA CCCACGCCUGCGUGCCUACAGAUCCAAACCCCCAG GAGAUGGAGCUGAAGAAUGUGACCGAGAACUUCAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCAGCCUGUGGGAUCAGUCCCUGAAG CCCUGCGUGAAGCUGACACCUCUGUGCGUGACCCU GGAUUGUACAAAUAUCAACAGCACAAACUCCACCA ACAAUACAAGCUCCAAUUCUAAGAUGGAGGAGACA AUCGGCGUGAUCAAGAAUUGUAGCUUCAACGUGAC AACCAAUAUCCGGGACAAGGUGAAGAAGGAGAACG CCCUGUUUUACUCUCUGGAUCUGGUGAGCAUCGGC AAUUCUAACACCAGCUAUCGCCUGAUCUCCUGCAA UACCUCUAUCAUCACACAGGCCUGUCCAAAGGUGA GCUUCGACCCUAUCCCAAUCCACUACUGCGCACCA GCAGGAUUCGCAAUCCUGAAGUGUAGGGAUAAGAA GUUUAACGGCACCGGCCCUUGCAGAAACGUGAGCA GCGUGCAGUGUACACACGGCAUCAGGCCAGUGGUG AGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAGA GGAGGAGAUCAUCAUCAGAUCCGCCAACCUGACCG ACAAUGCCAAGACAAUCAUCAUCCAGCUGAACGAG ACAAUCCAGAUCAAUUGCACAAGGCCCAACAAUAA CACCGUGAGAAGCAUCCCAAUCGGCCCCGGCCGGA CCUUUUACUAUACAGGCGACAUCAUCGGCGAUAUC CGCAAGGCCUACUGUAACAUCUCCGCCACCAAGUG GAAUAACACACUGCGGCAGAUCGCCGAGAAGCUGC GCGAGAAGUUCAACAAGACAAUCAUCUUUGCCCAG UCCUCUGGCGGCGAUCCAGAGGUGGUGAGGCACAC CUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAACA GCUCCCAGCUGUUUAAUAGCACAUGGUAUUCCAAC GGCACCUCUAAUGGCGGCCUGAAUAACAGCGCCAA CAUCACCCUGCCCUGCAGAAUCAAGCAGAUCAUCA AUCUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCC CCUCCCAUCAAGGGCGUGAUCAACUGUCUGUCCAA UAUCACCGGCAUCAUCCUGACAAGGGACGGCGGCG AGAAUAACGGCACAACCGAGACAUUCAGACCCGGC GGCGGCGACAUGAGGGAUAACUGGCGCUCUGAGCU GUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGG GCAUCGCCCCAACCAAGUGCAAGAGGAGAGUGGUG GGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGG CGGCCACGCAGCAGUGGGCCUGGGAGCCGUGUCUC UGGGCUUUCUGGGCCUGGCAGGCUCCACAAUGGGA GCAGCCUCUGUGACACUGACCGUGCAGGCAAGGCU GCUGCUGAGCGGCAUCGUGCAGCAGCAGAAUAACC UGCUGAGGGCACCAGAGCCUCAGCAGCAGCUGCUG CAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGC CCGGGUGCUGGCCCUGGAGCACUACCUGAAGGAUC AGCAGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAG CUGAUCUGCUGUACAACCGUGCCAUGGAACGCCUC CUGGUCUAACAAGUCCUAUAAUCAGAUCUGGAAUA ACAUGACAUGGAUGAACUGGAGCAGGGAGAUCGAC AAUUACACCAACCUGAUCUAUAAUCUGAUUGAAGA GUCACAGUCACAGCAGGAAAAGAACAACCUGAGCC UGCUGCAGCUGGAC 398F1_HM215312_MD39_L14G8-nucleic acid (SEQ ID NO: 249) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGC CGCAACUAGAGUGCAUAGCAUGGGCAACCUGUGGG UCACCGUGUAUUACGGGGUGCCAGUGUGGAAGGAC GCCGAGACUACGCUGUUCUGCGCCUCCGAUGCCAA GGCCUACCACACAGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGACCCAAAUCCCCAG GAGAUCAACCUGGAGAAUGUGACCGAGGAGUUUAA CAUGUGGAAGAAUAAGAUGGUGGAGCAGAUGCACG AGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAG CCUUGCGUGCAGCUGACCCCACUGUGCGUGACACU GGACUGUCAGUACAACGUGACCAACAUCAAUAGCA CAUCCGAUAUGGCCAGGGAGAUCAACAAUUGUAGC UAUAAUAUCACCACAGAGCUGCGGGAUCGCGAGCA GAAAGUGUACAGCCUGUUCUAUAGGUCCGACAUCG UGCAGAUGAACUCCGAUAAUAGCUCCAAGUACAGA CUGAUCAACUGCAAUACCUCUGCCAUCAAGCAGGC CUGUCCAAAGGUGACAUUUGAGCCUAUCCCAAUCC ACUAUUGCGCACCAGCAGGAUUCGCAAUCCUGAAG UGUAAGGACAAGGAGUUUAACGGCACCGGCCCUUG CAAGAACGUGAGCACCGUGCAGUGUACACACGGCA UCAAGCCAGUGGUGAGCACACAGCUGCUGCUGAAC GGCUCCCUGGCCGAGGAGAAAGUGAUCAUCCGGUC UGAGAAUAUCACCGAUAACGCCAAGAAUAUCAUCG UGCAGCUGAAGGAGCCCGUGAAGAUCAACUGCACC CGGCCUAACAAUAACACAGUGAAGUCCGUGCGCAU CGGCCCUGGCCAGACCUUCUACUAUACAGGCGAGA UCAUCGGCGACAUCCGCCAGGCCCACUGUAACGUG UCUAAGGCCCACUGGGAGAACACCCUGCAGGAGGU GGCCAAUCAGCUGAAGCUGAUGAUCCACAGCAACA AGACAAUCAUCUUCGCCAAUUCUAGCGGCGGCGAU CUGGAGAUCACCACACACUCUUUUAACUGCGGCGG CGAGUUCUUUUACUGUUAUACCAGCGGCCUGUUCA ACUACACCUUCAACGACACCAGCACAAACUCCACC GAGUCUAAGAGCAAUGAUACCAUCACACUGCAGUG CAGGAUCAAGCAGAUCAUCAACAUGUGGCAGAGAG CAGGACAGGCCGUGUAUGCCCCUCCCAUCCCCGGC AUCAUCCGGUGUGAGAGCAAUAUCACCGGCCUGAU CCUGACACGCGACGGCGGAAAUAACAAUUCCAACA CCAAUGAGACAUUCAGGCCCGGCGGCGGCGACAUG AGGGAUAACUGGAGAUCUGAGCUGUACAGAUAUAA GGUGGUGAAGAUCGAGCCAAUCGGCGUGGCCCCCA CCACAUGCAAGAGGAGAGUGGUGGGCUCCCACUCU GGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCAGC CGUGGGCAUCGGAGCCGUGAGCCUGGGCUUUCUGG GAGCAGCAGGCUCUACCAUGGGAGCAGCCAGCAUC ACCCUGACAGUGCAGGCAAGGCAGCUGCUGUCCGG AAUCGUGCAGCAGCAGUCUAACCUGCUGAGGGCAC CAGAGCCUCAGCAGCACCUGCUGAAGGACACCCAC UGGGGCAUCAAGCAGCUGAAGGCCAGGGUGCUGGC CGUGGAGCACUACCUGAAGGAUCAGCAGCUGCUGG GCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGU ACCAACGUGCCCUGGAAUUCCUCUUGGUCUAACAA GAGCCUGGGCGAGAUCUGGGACAACAUGACCUGGC UGAAUUGGUCCAAGGAGAUCGAGAAUUACACACAG AUCAUCUAUGAGCUGAUUGAAGAGUCACAGAACCA GCAGGAGAAAAACAACCAGAGCCUGCUGGCACUGG AU 246F3_HM215279_MD39_L14G8-nucleic acid (SEQ ID NO: 250) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGC CGCUACUCGGGUGCACUCUAUGCAGGACCUGUGGG UGACCGUCUAUUAUGGGGUGCCAGUGUGGAAGGAC GCCAAGACCACACUGUUCUGCGCCUCCGAUGCCAA GGCCUACGAGAAGGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGACCCAAACCCCCAG GAGAUCGUGAUGGCCAAUGUGACCGAGGAGUUUAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCUCUCUGUGGGAUCAGAGCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACU GGACUGUAAGGAUUACAACUAUUCCAUCACCAACA AUUCUACAGGCAUGGAGGGCGAGAUCAAGAAUUGU UCUUAUAACAUCACCACAGAGCUGCGCGACAAGAG GCAGAAAGUGUACAGCCUGUUCUAUCGCCUGGAUG UGGUGCAGAUCAAUGACUCUAACGAUCGCAACAAU AGCCAGUACAGGCUGAUCAAUUGCAACACCACAAC CAUGACCCAGGCCUGUCCUAAGGUGACAUUUGACC CUAUCCCAAUCCACUAUUGCGCCCCAGCCGGCUUC GCCAUCCUGAAGUGUAACAAUAAGACCUUUAAUGG CAAGGGCCCCUGCAACAAUGUGAGCUCCGUGCAGU GUACCCACGGCAUCAAGCCUGUGGUGUCUACACAG CUGCUGCUGAACGGCAGCCUGGCCGAGAAGGAGAU CAUCAUCAGGAGCGAGAAUCUGACCGACAACGUGA AGACAAUCAUCGUGCACCUGAAUGAGAGCGUGGAG AUCAACUGCACCAGACCAAACAAUAACACAGUGAA GUCCGUGCGGAUCGGACCAGGACAGACCUUCUACU AUACAGGCGAUAUCAUCGGCAAUAUCCGCCAGGCC CACUGUACCGUGAAUAAGACAGAGUGGAACACAGC CCUGACCAGGGUGAGCAAGAAGCUGAAGGAGUACU UCCCCAACAAGACCAUCGCCUUUCAGCCUUCUAGC GGCGGCGACCUGGAGAUCACAACCUUCUCCUUUAA UUGCAGAGGCGAGUUCUUUUAUUGUAACACAUCCG AUCUGUUCAAUGGCACCUUUAACGAGACAUCUGGC CAGUUCAAUUCCACCUUUAACUCUACACUGCAGUG CCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAG UGGGACAGGCAAUGUACGCCCCUCCCAUCGCAGGC AGCAUCACCUGUAUCUCCAACAUCACCGGCCUGAU CCUGACACGCGACGGCGGAAAUACAAACUCCACCA AGGAGACAUUCAGGCCUGGCGGCGGCAAUAUGAGA GAUAACUGGCGGUCUGAGCUGUACAAGUAUAAGGU GGUGAAGAUCGAGCCACUGGGAGUGGCACCAACCA AGUGCAGGAGACGGGUGGUGGGCAGCCACUCCGGC UCUGGCGGCAGCGGCUCCGGCGGCCACGCAGCAGU GGGCAUCGGCGCCGUGUCUAUCGGCUUUCUGGGAG CAGCAGGCUCCACCAUGGGAGCAGCCUCUAUCACA CUGACCGUGCAGGCCAGACAGCUGCUGAGCGGCAU CGUGCAGCAGCAGUCCAACCUGCUGAGGGCACCAG AGCCUCAGCAGCACCUGCUGAAGGACACCCACUGG GGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGU GGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCA UCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACA AAUGUGCCCUGGAACUCCUCUUGGUCUAACAAGAG CCAGGACGAGAUCUGGGAUAAUAUGACCUGGCUGA ACUGGAGCAAGGAGAUCUCCAAUUACACACAGAUC AUCUAUAACCUGAUUGAAGAAUCACAGACUCAGCA GGAACUGAAUAAUAGGUCACUGCUGGCACUGGAU CE0217_FJ443575_MD39_L14G8 (SEQ ID NO: 251) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCCGC CGCAACUCGCGUGCAUUCAGCAAAAGAUAUGUGGG UCACCGUCUAUUAUGGAGUGCCCGUGUGGCGGGAG GCCAAGACCACACUGUUUUGCGCAAGCGACGCAAA GGCAUACGAGAGGGAGGUGCACAACGUGUGGGCCA CACACGCCUGCGUGCCAACCGAUCCAAAUCCCCAG GAGAGAGUGCUGGAGAACGUGACCGAGAAUUUCAA CAUGUGGAAGAACAAUAUGGUGGACCAGAUGCACG AGGAUAUCAUCUCUCUGUGGGACGAGAGCCUGAAG CCCUGCAUCAAGCUGACACCUCUGUGCGUGACCCU GAAUUGUGGCAACGCCAUCGUGAAUGAGUCCACCA UCGAGGGCAUGAAGAAUUGUUCUUUUAACGUGACC ACAGAGCUGAAGGACAAGAAGAAGAAGGAGUACGC CCUGUUCUAUAAGCUGGAUGUGGUGCCCCUGAACG GCGAGAACAACAACUCUAACAGCAAGAACUUUAGC GAGUACAGGCUGAUCAAUUGCAACACCUCCACAAU CACCCAGGCCUGUCCCAAGGUGUCUUUCGAUCCUA UCCCAAUCCACUAUUGCGCCCCUGCCGGCUUCGCC AUCCUGAAGUGUAAUAACGAGACAUUCAACGGCAC CGGCCCAUGCAAUAACGUGUCCACAGUGCAGUGUA CCCACGGCAUCAAGCCCGUGGUGUCUACACAGCUG CUGCUGAAUGGCAGCCUGGCCGAGAAGGAGAUCAU CAUCAGGUCUGAGAACCUGACCAAUAACGCCAAGA UCAUCAUCGUGCACCUGAAUAACCCAGUGAAGAUC AUCUGCACAAGGCCCGGCAAUAACACCGUGAAGAG CAUGAGAAUCGGCCCUGGCCAGACAUUCUACUAUA CCGGCGACAUCAUCGGCGAUAUCAGGAGAGCCUAC UGUAACAUCUCUGAGAAGACAUGGUAUGACACCCU GAAGAAUGUGAGCGAUAAGUUCCAGGAGCACUUUC CUAACGCCUCCAUCGAGUUCAAGCCAUCUGCCGGC GGCGACCUGGAGAUCACCACACACUCCUUUAAUUG CAGGGGCGAGUUCUUUUACUGUGAUACAAGCGAGC UGUUCAAUGGCACAUACAAUAACUCCACCUAUAAC AGCUCCAAUAACAUCACCCUGCAGUGCAAGAUCAA GCAGAUCAUCAACAUGUGGCAGGGCGUGGGCAGAG CCAUGUAUGCCCCUCCCAUCGCCGGCAAUAUCACC UGUGAGAGCAACAUCACAGGCCUGCUGCUGACCCG GGACGGCGGAAAUAACAAGUCCACACCAGAGACAU UCAGGCCCGGCGGCGGCGACAUGAGGGAUAACUGG AGAAGCGAGCUGUACAAGUAUAAGGUGGUGGAGAU CAAGCCUCUGGGCAUCGCCCCAACAAAGUGCAAGA GGAGGGUGGUGGGCUCCCACUCUGGCAGCGGCGGC UCCGGCUCUGGCGGCCACGCAGCCGUGGGCAUGGG CGCCGUGUCUCUGGGCUUCCUGGGAGCAGCAGGCA GCACCAUGGGAGCAGCAUCCCUGACACUGACCGUG CAGGCAAGGCAGCUGCUGAGCGGCAUCGUGCAGCA GCAGAAUAACCUGCUGAGAGCCCCCGAGCCUCAGC AGCACAUGCUGCAGGACACACACUGGGGCAUCAAG CAGCUGCAGGCCCGGGUGCUGGCAAUCGAGCACUA CCUGACAGAUCAGCAGCUGCUGGGCAUCUGGGGCU GUUCCGGCAAGCUGAUCUGCUGUACCAAUGUGCCC UGGAAUAACAGCUGGUCCAACAAGUCCUAUGAGGA UAUCUGGGGCCGGAAUAUGACCUGGAUGAACUGGA GCAGGGAGAUCAACAACUACACAAACACCAUCUAU CGCCUGCUGGAAAAGUCACAGAAUCAGCAGGAGAA GAAUAAUAAGUCACUGCUGGAACUGGAC CE1176_FJ444437_MD39_L14G8-RNA (SEQ ID NO: 252) AUGGAUUGGACUUGGAUUCUGUUUCUGGUCGCCGC CGCUACUCGCGUGCAUUCAGUGGGCAACCUGUGGG UCACCGUCUACUAUGGGGUGCCCGUGUGGAAGGAG GCCAAGACCACACUGUUCUGCGCCUCCGACGCCAA GGCCUACGAGAAGGAGGUGCACAACGUGUGGGCCA CACACGCCUGCGUGCCUACCGAUCCAAAUCCCCAG GAGAUGGUGCUGGAGAACGUGACAGAGAACUUUAA UAUGUGGAAGAACGACAUGGUGGAUCAGAUGCACG AGGACGUGAUCUCUCUGUGGGAUCAGAGCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACCCU GACAUGUACCAAUACCACAGUGUCCAACGGCAGCU CCAACUCUAAUGCCAACUUCGAGGAGAUGAAGAAU UGUUCUUUUAACGCCACCACAGAGAUCAAGGACAA GAAGAAGAACGAGUACGCCCUGUUCUAUAAGCUGG AUAUCGUGCCCCUGAACAAUUCUAGCGGCAAGUAU AGGCUGAUCAAUUGCAACACAAGCGCCAUCGCCCA GGCCUGUCCAAAGGUGACCUUCGAGCCUAUCCCAA UCCACUACUGCGCCCCCGCCGGCUAUGCCAUCCUG AAGUGUAACAACAAGACCUUCAACGGCACCGGCCC UUGCAACAACGUGAGCACAGUGCAGUGUACCCACG GCAUCAAGCCAGUGGUGAGCACCCAGCUGCUGCUG AACGGCUCCCUGGCAGAGAAGGAGAUCAUCAUCCG GAGCGAGAAUCUGACAAACAAUGCCAAGACCAUCA UCAUCCACCUGAACGAGUCCGUGGGCAUCGUGUGC ACACGGCCCAGCAACAAUACCGUGAAGUCCAUCCG CAUCGGCCCUGGCCAGACCUUCUACUAUACCGGCG ACAUCAUCGGCGAUAUCCGCCAGGCCCACUGUAAU GUGAGCAAGCAGAAUUGGAACAGGACACUGCAGCA AGUGGGCAGAAAGCUGGCCGAGCACUUCCCAAAUA GGAACAUCACCUUUGCCCACUCCUCUGGCGGCGAC CUGGAGAUCACCACACACUCCUUCAACUGCAGAGG CGAGUUCUUUUACUGUAAUACAUCUGGCCUGUUUA ACGGCACCUACCACCCCAAUGGCACAUAUAACGAG ACAGCCGUGAAUAGCUCCGAUACAAUCACCCUGCA GUGCAGGAUCAAGCAGAUCAUCAACAUGUGGCAGG AAGUGGGCAGAGCCAUGUAUGCCCCUCCCAUCGCC GGCAAUAUCACCUGUAACAGCACAAUCACCGGCCU GCUGCUGACACGGGACGGCGGCAUCAACCAGACCG GAGAGGAGAUCUUCCGCCCCGGCGGCGGCGACAUG CGGGAUAAUUGGCGCAACGAGCUGUACAAGUAUAA GGUGGUGGAGAUCAAGCCACUGGGCAUCGCCCCCA CAAAGUGCAAGAGGAGAGUGGUGGGCUCCCACUCU GGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCAGC CGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGG GAGCAGCAGGCUCUACCAUGGGAGCAGCCAGCAUC ACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGG CAUCGUGCAGCAGCAGUCUAACCUGCUGAGAGCCC CCGAGCCUCAGCAGCACAUGCUGCAGGACACCCAC UGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGC CAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUGG GCAUCUGGGGCUGUUCUGGCAAGCUGAUCUGCUGU ACAAAUGUGCCAUGGAACUCUAGCUGGAGCAACCG GUCCCAGGAGGACAUCUGGAACAAUAUGACCUGGA UGAAUUGGAGCAGGGAGAUCGAUAACUACACACAC ACCAUCUAUAGCCUGCUGGAGGAGUCACAGAUUCA GCAGGAGAAAAAUAAUAAGUCACUGCUGGCACUGG AC 25710_EF117271_MD39_L14G8-RNA (SEQ ID NO: 253) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGC CGCUACUCGCGUGCAUUCUGGGGGCAACCUGUGGG UCACCGUGUAUUAUGGAGUGCCCGUGUGGAAGGAG GCCACCACAACCCUGUUCUGCGCCAGCGACGCCAA GGCCUACGAUAAGGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGACCCAAACCCCCAG GAGAUGGUGCUGGGCAAUGUGACCGAGAACUUUAA UAUGUGGAAGAACGAGAUGGUGAAUCAGAUGCACG AGGACGUGAUCUCCCUGUGGGAUCAGUCUCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACU GGAGUGUUCCAACGUGACCUAUAAUGAGUCUAUGA AGGAGGUGAAGAACUGUUCCUUCAAUCUGACAACC GAGCUGAGGGAUAAGAAGCAGAAGGUGCACGCCCU GUUUUACAGACUGGACAUCGUGCCCCUGAACGAUA CCGAGAAGAAGAAUAGCUCCCGGCCUUAUCGCCUG AUCAACUGCAAUACAAGCGCCAUCACCCAGGCCUG UCCUAAGGUGACCUUCGACCCUAUCCCAAUCCACU ACUGCACACCAGCCGGCUAUGCCAUCCUGAAGUGU AACGAUAAGAAGUUUAAUGGCACCGGCCCAUGCCA CAAGGUGUCCACAGUGCAGUGUACCCACGGCAUCA AGCCCGUGGUGUCUACACAGCUGCUGCUGAACGGC AGCCUGGCAGAGGGCGAGAUCAUCAUCAGGAGCGA GAACCUGACCAACAAUGCCAAGACAAUCAUCGUGC ACCUGAAUCAGUCCGUGGAGAUCGUGUGCGCCCGG CCAAGCAACAAUACAGUGACCUCCAUCAGGAUCGG ACCAGGACAGACAUUCUACUAUACCGGCGCCAUCA CAGGCGACAUCAGGCAGGCCCACUGUAACAUCAGC AAGGAUAAGUGGAAUGAGACACUGCAGAGAGUGGG CGAGAAGCUGGCCGAGCACUUCCCCAACAAGACAA UCAAGUUUGCCUCUAGCUCCGGCGGCGACCUGGAG AUCACAACCCACUCCUUUAACUGCAGGGGCGAGUU CUUUUACUGUAAUACCUCUGGCCUGUUCAACGGCA CCUUUAAUGGCACAUACGUGAGCCCCAACAGCACC GAUUCCAAUUCUAGCUCCAUCAUCACAAUCCCUUG CCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAG UGGGAAGGGCAAUGUACGCCCCUCCCAUCGCCGGC AACAUCACCUGUAAGUCCAAUAUCACAGGCCUGCU GCUGGUGAGGGACGGCGGAACCGGCUCUGAGAGCA ACAAGACAGAGAUCUUCAGACCCGGCGGCGGCGAC AUGAGGGAUAAUUGGAGAUCUGAGCUGUACAAGUA UAAGGUGGUGGAGAUCAAGCCACUGGGCGUGGCCC CCACCAAGUGCAAGAGGAGAGUGGUGGGCUCCCAC UCUGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGC AGCCGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUC UGGGAGCAGCAGGCUCUACAAUGGGAGCAGCCAGC AUCACACUGACCGUGCAGGCAAGGCAGCUGCUGAG CGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGGG CACCAGAGCCUCAGCAGCACCUGCUGCAGGACACC CACUGGGGCAUCAAGCAGCUGCAGACACGGGUGCU GGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGC UGGGCAUCUGGGGCUGUUCUGGCAAGCUGAUCUGC UGUACCGCCGUGCCCUGGAACUAUAGCUGGUCCAA UCGCAGCCAGGACGAUAUCUGGGACAACAUGACAU GGAUGAAUUGGUCUAAGGAGAUCAGCAACUACACA AAUACCAUCUAUAAGCUGCUGGAAGAUAGUCAGAU UCAGCAGGAAAAGAACAAUAAGUCACUGCUGGCAC UGGAU BJOX2000_HM215364_MD39_L14G8-RNA (SEQ ID NO: 254) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGC AGCAACUCGGGUGCAUAGCGUCGGCAACCUGUGGG UCACUGUCUACUACGGGGUGCCCGUGUGGAAGGAG GCCACCACAACCCUGUUCUGCGCCAGCGACGCCAA GGCCUACGAUACCGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCUACAGACCCAGAUCCCCAG GAGAUGUUCCUGGAGAACGUGACAGAGAACUUCAA CAUGUGGAAGAACAAUAUGGUGGACCAGAUGCACG AGGAUGUGAUCAGCCUGUGGGACCAGUCCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACU GGAGUGUAAGAAUGUGAACAGCUCCUCUAGCGACA CCAAGAACGGCACAGAUCCUGAGAUGAAGAAUUGU UCUUUCAACGCCACAACCGAGCUGCGGGACCGCAA GCAGAAGGUGUACGCCCUGUUUUAUAAGCUGGAUA UCGUGCCACUGAAUGAGAAGAACUCCUCUGAGUAU CGGCUGAUCAAUUGCAACACAAGCACCAUCACACA GGCCUGUCCCAAGGUGACCUUCGACCCUAUCCCAA UCCACUACUGCACACCUGCCGGCUAUGCCAUCCUG AAGUGUAAUGAUGAGAAGUUUAACGGCACCGGCCC AUGCUCCAACGUGAGCACCGUGCAGUGUACACACG GCAUCAAGCCCGUGGUGAGCACACAGCUGCUGCUG AACGGCUCCCUGGCCGAGAAGGGCAUCAUCAUCCG CUCCGAGAAUCUGACCAACAAUGUGAAGACAAUCA UCGUGCACCUGAACCAGUCCGUGGAGAUCCUGUGC AUCCGGCCAAACAAUAACACCGUGAAGUCUAUCCG CAUCGGCCCCGGCCAGACCUUCUACUAUACAGGCG AGAUCAUCGGCGACAUCCGGCAGGCCCACUGUAAU AUCUCUGGCAAGGUCUGGAACGAGACACUGCAGAG GGUGGGAGAGAAGCUGGCAGAGUACUUCCCAAACA AGACAAUCAAGUUUGCCAGCUCCUCUGGCGGCGAU CUGGAGAUCACAACCCACUCUUUUAAUUGCGGCGG CGAGUUCUUUUACUGUAACACCAGCAAGCUGUUCA AUGGCACCUUUAACGGCACAUAUAUGCCUAAUGUG ACCGAGGGCAACAGCACAAUCUCCAUCCCAUGCCG GAUCAAGCAGAUCAUCAAUAUGUGGCAGAAAGUGG GCCGCGCCAUGUAUGCCCCUCCCAUCGAGGGCAAC AUCACCUGUAAGAGCAAGAUCACAGGCCUGCUGCU GGAGAGGGACGGCGGACCAGAGAACGAUACCGAGA UCUUCAGACCCGGCGGCGGCGACAUGAGGAAUAAC UGGAGAUCCGAGCUGUACAAGUAUAAGGUGGUGGA GAUCAAGCCACUGGGAGUGGCACCAACCGAGUGCA AGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGC GGCUCUGGCAGCGGCGGCCACGCCGCCGUGGGCAU CGGAGCCGUGAGCCUGGGCUUUCUGGGAGUGGCAG GCUCUACCAUGGGAGCAGCAAGCAUGGCACUGACA GUGCAGGCCAGGCAGCUGCUGUCCGGCAUCGUGCA GCAGCAGUCUAAUCUGCUGAGAGCACCAGAGCCUC AGCAGCACCUGCUGCAGGACACCCACUGGGGCAUC AAGCAGCUGCAGACAAGGGUGCUGGCCAUCGAGCA CUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGG GCUGUUCCGGCAAGCUGAUCUGCUGUACCGCCGUG CCUUGGAAUAGCUCCUGGUCUAACAAGAGCCAGGA GGAGAUCUGGGAGAAUAUGACAUGGAUGAACUGGU CCAAGGAGAUCUCUAACUACACCGAUACAAUCUAU AGACUGCUGGAAGAUAGUCAGAAUCAGCAGGAGAG AAAUAAUAAGUCACUGCUGGCACUGGAU CH119_EF117261_MD39_L14G8-RNA (SEQ ID NO: 255) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGC CGCAACUCGCGUGCAUUCCGUGGGCAACCUGUGGG UCACCGUCUACUAUGGGGUGCCAGUGUGGAAGGAG GCCACCACAACCCUGUUCUGCGCCUCCGACGCCAA GGCCUACGAUACCGAGGUGCACAACGUGUGGGCAA CACACGCAUGCGUGCCAACCGACCCAUCUCCCCAG GAGCUGGUGCUGGAGAAUGUGACAGAGAACUUCAA CAUGUGGAAGAAUGAGAUGGUGAACCAGAUGCACG AGGACGUGAUCUCCCUGUGGGAUCAGUCUCUGAAG CCUUGCGUGAAGCUGACACCACUGUGCGUGACCCU GGAGUGUUCCAAGGUGUCUAACAAUGAGACAGACA AGUAUAACGGCACCGAGGAGAUGAAGAAUUGUAGC UUCAACGCAACAACCGUGGUGCGGGACCGCCAGCA GAAGGUGUACGCCCUGUUUUAUAGGCUGGAUAUCG UGCCCCUGACCGAGAAGAAUAGCUCCGAGAACUCU AGCAAGUACUAUAGACUGAUCAAUUGCAACACAUC UGCCAUCACCCAGGCCUGUCCAAAGGUGAGCUUCG AGCCUAUCCCAAUCCACUACUGCACCCCCGCCGGC UAUGCCAUCCUGAAGUGUAAUGACAAGACCUUCAA CGGCACCGGCCCUUGCCACAACGUGAGCACAGUGC AGUGUACCCACGGCAUCAAGCCAGUGGUGAGCACA CAGCUGCUGCUGAAUGGCUCCCUGGCCGAGGGCGA GAUCAUCAUCCGGUCCGAGAACCUGACAAACAAUG UGAAGACCAUCCUGGUGCACCUGAAUCAGAGCGUG GAGAUCGUGUGCACACGGCCCAACAAUAACACCGU GAAGUCCAUCCGCAUCGGCCCUGGCCAGACAUUCU ACUAUACCGGCGACAUCAUCGGCGAUAUCCGGCAG GCCCACUGUAACAUCUCCAAGUGGCACGAGACACU GAAGCGCGUGUCUGAGAAGCUGGCCGAGCACUUCC CUAAUAAGACAAUCAACUUUACCUCCUCUAGCGGC GGCGACCUGGAGAUCACAACCCACUCUUUCACCUG CCGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCC UGUUUAACUCCACAUACAUGCCCAAUGGCACCUAU CUGCACGGCGAUACAAAUUCCAACUCCUCUAUCAC CAUCCCUUGCAGGAUCAAGCAGAUCAUCAACAUGU GGCAGGAAGUGGGCAGAGCCAUGUAUGCCCCUCCC AUCGAGGGCAACAUCACCUGUAAGUCUAAUAUCAC AGGCCUGCUGCUGGUGCGGGACGGCGGAACCGAGA GCAAUAACACAGAGACAAAUAACACAGAGAUCUUC CGCCCCGGCGGCGGCGACAUGAGGGAUAACUGGAG AAGCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCA AGCCACUGGGAGUGGCACCAACCGCAUGCAAGAGG AGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUC UGGCAGCGGCGGCCACGCCGCCGUGGGCAUCGGAG CCGUGUCCCUGGGCUUUCUGGGAGUGGCAGGCUCU ACCAUGGGAGCAGCCAGCAUGACACUGACCGUGCA GGCAAGGCAGCUGCUGUCCGGCAUCGUGCAGCAGC AGUCUAACCUGCUGAGAGCACCAGAGCCUCAGCAG CACCUGCUGCAGGACACCCACUGGGGCAUCAAGCA GCUGCAGACACGGGUGCUGGCCAUCGAGCACUACC UGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGU AGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCUUG GAAUAGCUCCUGGAGCAACAAGUCCCAGAAGGAGA UCUGGGAUAAUAUGACAUGGAUGAACUGGUCUAAG GAGAUCAGCAAUUACACAAACACCAUCUAUAAGCU GCUGGAGGACUCACAGAAUCAGCAGGAAUCAAACA ACAAAUCCCUGCUGGCACUGGAC X1632_FJ817370_MD39_L14G8-RNA (SEQ ID NO: 256) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGC CGCUACACGGGUGCAUUCAUCAAAUAACCUGUGGG UCACUGUCUACUAUGGGGUGCCCGUGUGGGAGGAC GCCGAUACCACACUGUUCUGCGCAUCCGACGCAAA GGCAUACUCCACCGAGUCUCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGACCCAAACCCCCAG GAGAUCUAUCUGGAGAACGUGACAGAGGACUUCAA CAUGUGGGAGAACAAUAUGGUGGAGCAGAUGCAGG AGGACAUCAUCAGCCUGUGGGAUGAGUCCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACU GACCUGUACAAAUGUGACCAACGUGACAGACUCUG UGGGCACAAAUAGCCGCCUGAAGGGCUACAAGGAG GAGCUGAAGAACUGUAGCUUCAAUACCACAACCGA GAUCAGGGAUAAGAAGAAGCAGGAGUACGCCCUGU UUUAUAAGCUGGACAUCGUGCCAAUCAAUGAUAAC AGCAACAAUUCCAACGGCUACAGACUGAUCAAUUG CAACGUGUCCACCAUCAAGCAGGCCUGUCCAAAGG UGUCUUUCGACCCUAUCCCAAUCCACUAUUGCGCA CCAGCAGGAUUCGCAAUCCUGAAGUGUCGCGAUAA GGAGUUUAAUGGCACCGGCACAUGCAGGAACGUGA GCACCGUGCAGUGUACACACGGCAUCAAGCCCGUG GUGUCUACCCAGCUGCUGCUGAAUGGCAGCCUGGC CGAGGGCGACAUCAUCAUCAGAUCCGAGAACAUCA CCGAUAAUGCCAAGACAAUCAUCGUGCACCUGAAC AAGACCGUGAGCAUCACCUGCACACGCCCCAACAA UAACACAGUGAAGUCCAUCAGGAUCGGCCCUGGCC AGGCCCUGUACUAUACCGGAGCAAUCAUCGGCGAC ACAAGGCAGGCCCACUGUAAUAUCAACGGCUCCGA GUGGUACGAGAUGAUCCAGAAUGUGAAGAACAAGC UGAAUGAGACAUUCAAGAAGAACAUCACAUUUGCC CCCAGCUCCGGCGGCGAUCUGGAGAUCACAACCCA CUCUUUUAACUGCCGCGGCGAGUUCUUUUAUUGUA ACACCAGCGAGCUGUUCAAUUCUAGCCACCUGUUU AACGGCUCUACCCUGAGCACAAACGGCACCAUCAC ACUGCCUUGCAGGAUCAAGCAGAUCGUGCGCAUGU GGCAGAGGGUGGGACAGGCAAUGUACGCCCCUCCC AUCGCCGGCAAUAUCACCUGUAGAUCUAACAUCAC CGGCCUGCUGCUGACACGGGACGGCGGAACCAACA AGGAUACAAAUGAGGCAGAGACAUUCAGACCCGGC GGCGGCGACAUGAGAGAUAACUGGCGGAGCGAGCU GUACAAGUAUAAGGUGGUGAAGAUCAAGCCACUGG GAGUGGCACCAACCAGGUGCAGGAGACGGGUGGUG GGCAGCCACUCCGGCUCUGGCGGCAGCGGCUCCGG CGGCCACGCAGCAAUCGGCCUGGGCACCGUGAGCC UGGGCUUUCUGGGAACCGCAGGCUCCACAAUGGGA GCAGCCUCUAUCACCCUGACAGUGCAGGUGAGACA GCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACC UGCUGAGGGCACCAGAGCCUCAGCAGCACCUGCUG CAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGC CCGCGUGCUGGCAGUGGAGCACUACCUGAAGGAUC AGCAGAUCCUGGGCAUCUGGGGCUGUUCCGGCAAG CUGAUCUGCUGUACCAACGUGCCCUGGAAUUCCUC UUGGUCUAAUAAGUCUUAUAGCGACAUCUGGGAUA ACCUGACAUGGAUCAAUUGGUCCAGGGAGAUCUCU AACUACACCCAGCAGAUCUAUACACUGCUGGAAGA AAGUCAGAAUCAGCAGGAGAAGAAUAAUCAGAGCC UGCUGGCACUGGAU CNE8_HM215427_MD39_L14G8-RNA (SEQ ID NO: 257) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGC UGCUACACGAGUGCAUUCAUCUGAUAACCUGUGGG UCACCGUCUACUAUGGCGUGCCAGUGUGGCGGGAC GCCGAUACCACACUGUUCUGCGCCAGCGACGCCAA GGCCUACGAUACCGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGACCCUAAUCCACAG GAGAUCCACCUGGAGAACGUGACAGAGAACUUCAA CAUGUGGAAGAACAAGAUGGCCGAGCAGAUGCAGG AGGACGUGAUCUCCCUGUGGGAUGAGUCUCUGAAG CCCUGCGUGCAGCUGACCCCUCUGUGCGUGACACU GAAUUGUACCAAUGCCAACCUGAAUGCCACCGUGA AUGCCUCCACCACAAUCGGCAACAUCACAGAUGAG GUGCGGAACUGUUCUUUCAAUACCACAACCGAGCU GCGCGACAAGAAGCAGAACGUGUACGCCCUGUUUU AUAAGCUGGAUAUCGUGCCCAUCAACAAUAACUCC GAGUAUCGGCUGAUCAACUGCAAUACCUCUGUGAU CAAGCAGGCCUGUCCUAAGGUGAGCUUCGACCCCA UCCCUAUCCACUACUGCGCACCAGCAGGAUAUGCA AUCCUGCGCUGUAAUGAUAAGAACUUUAAUGGCAC AGGCCCCUGCAAGAACGUGAGCUCCGUGCAGUGUA CCCACGGCAUCAAGCCUGUGGUGUCUACACAGCUG CUGCUGAACGGCAGCCUGGCCGAGGACGAGAUCAU CAUCAGGAGCGAGAACCUGACAGAUAAUGUGAAGA CCAUCAUCGUGCACCUGAACAAGUCCGUGGAGAUC AAUUGCACCAGGCCAUCUAAUAACACAGUGACCAG CGUGAGAAUCGGCCCCGGCCAGGUGUUCUACUAUA CAGGCGACAUCAUCGGCGAUAUCCGGAAGGCCUAC UGUGAGAUCAAUCGCACAAAGUGGCACGAGACACU GAAGCAGGUGGCCACCAAGCUGAGGGAGCACUUCA ACAAGACAAUCAUCUUUCAGCCCCCUUCCGGCGGC GACAUCGAGAUCACCAUGCACCACUUCAACUGCAG AGGCGAGUUCUUUUACUGUAACACAACCAAGCUGU UUAAUUCUACCUGGGGCGAGAACACAACCAUGGAG GGCCACAAUGAUACAAUCGUGCUGCCUUGCAGAAU CAAGCAGAUCGUGAACAUGUGGCAGGGAGUGGGAC AGGCAAUGUAUGCCCCACCCAUCAGGGGCAGCAUC AACUGCGUGAGCAAUAUCACAGGCAUCCUGCUGAC CAGAGACGGCGGAACAAACAUGUCUAAUGAGACAU UCAGGCCUGGCGGCGGCAACAUCAAGGAUAAUUGG AGAAGCGAGCUGUACAAGUAUAAGGUGGUGGAGAU CGAGCCUCUGGGCAUCGCCCCAACAAAGUGCAAGA GGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGC UCUGGCAGCGGCGGCCACGCCGCCGUGGGCAUCGG CGCCAUGAGCUUCGGCUUUCUGGGAGCAGCAGGCU CCACCAUGGGAGCAGCCUCUAUCACACUGACCGUG CAGGCAAGGCAGCUGCUGAGCGGCAUCGUGCAGCA GCAGUCCAACCUGCUGAGGGCACCAGAGCCACAGC AGCACCUGCUGCAGGACACCCACUGGGGCAUCAAG CAGCUGCAGGCCCGCGUGCUGGCAGUGGAGCACUA CCUGAAGGAUCAGAAGUUUCUGGGCCUGUGGGGCU GUUCCGGCAAGAUCAUCUGCUGUACCGCCGUGCCU UGGAACUCCACAUGGUCUAAUCGGAGCUAUGAGGA GAUCUGGGACAACAUGACCUGGAUCAAUUGGUCCC GCGAGAUCUCUAACUACACAAGCCAGAUCUAUGAG AUCCUGACCGAAUCACAGAAUCAGCAGGACAGAAA CAACAAAUCACUGCUGGAACUGGAC CNE55_HM215418_MD39_L14G8-RNA (SEQ ID NO: 258) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCUGC CGCUACACGAGUGCAUUCCUCUGAUAAACUGUGGG UGACCGUCUACUAUGGAGUGCCAGUGUGGCGGGAC GCCGAUACCACACUGUUCUGCGCCUCUGACGCCAA GGCCCACGAGACAGAGGUGCACAACGUGUGGGCAA CCCACGCAUGCGUGCCAACAGAUCCUAACCCACAG GAGAUCCACCUGGUGAAUGUGACAGAGAACUUUAA UAUGUGGAAGAACAAGAUGGUGGAGCAGAUGCAGG AGGACGUGAUCAGCCUGUGGGAUGAGUCCCUGAAG CCCUGCGUGAAGCUGACCCCUCUGUGCGUGACACU GAACUGUACCACAGCCAACACCAAUGAGACAAAGA ACAAUACCACAGACGAUAAUAUCAAGGACGAGAUG AAGAACUGUACCUUCAAUAUGACCACAGAGAUCCG GGACAAGAAGCAGCGCGUGAGCGCCCUGUUUUACA AGCUGGAUAUCGUGCCCAUCGACGAUAGCAAGAAC AAUUCCGAGUAUCGCCUGAUCAACUGCAAUACCAG CGUGAUCAAGCAGGCCUGUCCUAAGGUGUCCUUCG ACCCCAUCCCUAUCCACUACUGCACCCCAGCCGGC UAUGUGAUCCUGAAGUGUAACGAUAAGAACUUUAA UGGCACAGGCCCCUGCAAGAAUGUGAGCUCCGUGC AGUGUACCCACGGCAUCAAGCCUGUGGUGUCCACA CAGCUGCUGCUGAACGGCUCUCUGGCCGAGGAGGA GAUCAUCAUCAGGUCUGAGAAUCUGACCGAUAACG CCAAGAAUAUCAUCGUGCACCUGAACAAGAGCGUG GAGAUCAAUUGCACACGGCCAUCUAACAAUACCGU GACAAGCGUGCGCAUCGGACCAGGACAGGUGUUCU ACUAUACCGGCGACAUCACAGGCGAUAUCAGAAAG GCCUACUGUGAGAUCGACGGCACCGAGUGGAACAA GACCCUGACACAGGUGGCCGAGAAGCUGAAGGAGC ACUUUAAUAAGACCAUCGUGUACCAGCCCCCUUCC GGCGGCGAUCUGGAGAUCACAAUGCACCACUUCAA CUGCCGGGGCGAGUUCUUUUAUUGUAAUACCACAC AGCUGUUUAACAAUUCUGUGGGCAACAGCACCAUC AAGCUGCCUUGCCGCAUCAAGCAGAUCAUCAAUAU GUGGCAGGGAGUGGGACAGGCAAUGUACGCCCCAC CCAUCAGCGGAGCCAUCAACUGUCUGUCCAAUAUC ACCGGCAUCCUGCUGACAAGGGACGGCGGCGGAAA CAAUAGGUCCAAUGAGACAUUCAGGCCUGGCGGCG GCAACAUCAAGGAUAAUUGGAGAUCUGAGCUGUAC AAGUAUAAGGUGGUGGAGAUCGAGCCUCUGGGCAU CGCCCCAACAAAGUGCAAGAGGAGAGUGGUGGGCU CUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGC CACGCCGCCGUGGGCAUCGGCGCCAUGAGCUUCGG CUUUCUGGGAGCAGCAGGCUCCACCAUGGGAGCAG CCUCUAUCACCCUGACAGUGCAGGCCCGGCAGCUG CUGUCUGGCAUCGUGCAGCAGCAGAGCAACCUGCU GAGGGCACCAGAGCCACAGCAGCACAUGCUGCAGG ACACACACUGGGGCAUCAAGCAGCUGCAGGCCAGG GUGCUGGCAGUGGAGCACUACCUGAAGGAUCAGAG AUUUCUGGGCCUGUGGGGCUGUAGCGGCAAGACCA UCUGCUGUACAGCCGUGCCUUGGAACUCCACCUGG UCUAAUAAGACAUAUGAGGAGAUCUGGGACAACAU GACCUGGACAAAUUGGUCCCGGGAGAUCUCUAACU ACACCAAUCAGAUCUAUUCCAUUCUGACCGAAUCA CAGUCACAGCAGGAUAAAAAUAACAAAAGUCUGCU GGAACUGGAU AD8_MD64_link14_TS1-RNA (SEQ ID NO: 259) GGAUCCGCCACCAUGGACUGGACUUGGAUUCUGUU CCUGGUCGCCGCCGCUACUCGGGUGCAUUCUGUCG AAAACCUGUGGGUGACUGUCUAUUAUGGAGUGCCC GUGUGGAAGGAGGCCACCACAACCCUGUUCUGCGC CUCCGACGCCAAGGCCUACGAUACCGAGGUGCACA ACGUGUGGGCCACCCACGAGUGCGUGCCUACAGAC CCAAACCCCCAGGAGGUGGUGCUGGAGAAUGUGAC AGAGAACUUCAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCGAGCUGUGGGAU CAGAGCCUGAAGCCUUGCGUGAAGCUGACCCCACU GUGCGUGACCCUGAAUUGUACAGACCUGCGGAAUG UGACAAACAUCAACAAUAGCUCCGAGGGCAUGAGA GGCGAGAUCAAGAAUUGUAGCUUCAACAUCACAAC CUCCAUCAGGGACAAGGUGAAGAAGGAUUACGCCC UGUUUUAUCGCCUGGAUGUGGUGCCCAUCGACAAU GAUAACACCUCUUACCGGCUGAUCAAUUGCAACAC AAGCACCAUCACACAGGCCUGUCCAAAGGUGUCCU UCGAGCCUAUCCCAAUCCACUAUUGCACCCCCGCC GGCUUCGCCAUCCUGAAGUGUAAGGACAAGAAGUU UAACGGCACAGGCCCUUGCAAGAACGUGAGCACCG UGCAGUGUACACACGGCAUCCGGCCAGUGGUGAGC ACCCAGCUGCUGCUGAACGGCUCCCUGGCAGAGGA GGAAGUGAUCAUCAGAUCUAGCAAUUUCACAGAUA AUGCCAAGAACAUCAUCGUGCAGCUGAAGGAGUCC GUGGAGAUCAACUGCACCCGGCCCAACAAUAACAC AGUGAAGUCUAUCCACAUCGGCCCUGGCAGAGCCU UUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGG CAGGCCCACUGUAACAUCAGCCGCACCAAGUGGAA UAACACACUGAAUCAGAUCGCCACCAAGCUGAAGG AGCAGUUCGGCAAUAACAAGACAAUCGUGUUUAAC CAGUCCUCUGGCGGCGACCCAGAGAUCGUGAUGCA CUCUUUUAAUUGCGGCGGCGAGUUCUUUUACUGUA ACUCUACCCAGCUGUUCAAUAGCACAUGGAACUUC AACGGCACCUGGAAUCUGACACAGAGCAACGGCAC CGAGGGCAAUGAUACCAUCACACUGCCCUGCAGGA UCAAGCAGAUCAUCAACAUGUGGCAGGAAGUGGGC AAGGCCAUGUAUGCCCCUCCCAUCAGGGGCCAGAU CCGCUGUAGCUCCAAUAUCACCGGCCUGAUCCUGA CAAGGGACGGCGGAAAUAACCACAAUAACGAUACC GAGACAUUCCGCCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCCGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCACUGGGAGUGGCACCAACCAAG UGCAAGAGGAGAGUGGUGCAGUCUCACAGCGGCUC CGGCGGCUCUGGCAGCGGCGGCCACGCCGCCGUGG GCACCAUCGGCGCCAUGAGCCUGGGCUUUCUGGGA GCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUCAC CCUGACAGUGCAGGCCAGGCUGCUGCUGUCCGGCA UCGUGCAGCAGCAGAAUAACCUGCUGAGGGCACCA GAGCCUCAGCAGCACCUGCUGCAGCUGACCGUGUG GGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAG UGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGA AUCUGGGGAUGCAGCGGCAAGCUGAUCUGCUGUAC CGCCGUGCCAUGGAACGCCUCCUGGUCUAAUAAGA CCCUGGACAUGAUCUGGAAUAACAUGACAUGGAUG GAGUGGGAGCGCGAGAUCGAUAACUACACCGGCCU GAUCUAUACACUGAUCGAGGAAUCACAGAAUCAGC AGGAGAAAAACGAACAGGAACUGCUGGAACUGGAU GGCGGCGUCGAAAAUCUCUGGGUCACCGUCUAUUA UGGGGUCCCUGUCUGGAAGGAAGCAACUACUACUC UGUUCUGUGCCUCCGAUGCCAAGGCCUACGACACA GAGGUGCACAACGUGUGGGCUACACACGAGUGCGU GCCAACCGAUCCAAACCCCCAGGAGGUGGUGCUGG AGAACGUGACCGAGAACUUCAACAUGUGGAAGAAC AACAUGGUGGAGCAGAUGCACGAGGACAUCAUCGA GCUGUGGGAUCAGUCCCUGAAGCCUUGCGUGAAGC UGACACCACUGUGCGUGACACUGAACUGUACCGAC CUGAGGAACGUGACCAACAUCAACAACAGCUCCGA GGGAAUGAGAGGCGAGAUCAAGAACUGUAGCUUCA ACAUCACCACAUCCAUCCGGGACAAGGUGAAGAAG GAUUACGCCCUGUUUUACCGCCUGGAUGUGGUGCC CAUCGACAACGAUAACACCUCUUACAGGCUGAUCA ACUGCAACACCAGCACAAUCACCCAGGCUUGUCCA AAGGUGUCCUUUGAGCCUAUCCCAAUCCACUACUG CACACCCGCCGGCUUCGCUAUCCUGAAGUGUAAGG ACAAGAAGUUUAACGGAACCGGCCCUUGCAAGAAC GUGUCUACAGUGCAGUGUACCCACGGCAUCAGGCC AGUGGUGAGCACACAGCUGCUGCUGAACGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGAUCUAGCAAC UUCACCGAUAACGCUAAGAACAUCAUCGUGCAGCU GAAGGAGUCCGUGGAGAUCAACUGCACAAGGCCCA ACAACAACACCGUGAAGUCUAUCCACAUCGGACCU GGCAGAGCCUUUUACUACACAGGAGACAUCAUCGG CGAUAUCCGGCAGGCUCACUGUAACAUCAGCCGCA CAAAGUGGAACAACACCCUGAACCAGAUCGCCACA AAGCUGAAGGAGCAGUUCGGCAACAACAAGACCAU CGUGUUUAACCAGUCCAGCGGCGGCGACCCCGAGA UCGUGAUGCACUCUUUCAACUGCGGCGGAGAGUUC UUUUACUGUAACUCUACACAGCUGUUCAACAGCAC CUGGAACUUUAACGGAACAUGGAACCUGACCCAGA GCAACGGAACCGAGGGCAACGAUACAAUCACCCUG CCUUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GGAAGUGGGAAAGGCCAUGUACGCUCCCCCUAUCA GGGGACAGAUCAGGUGUAGCUCCAACAUCACAGGA CUGAUCCUGACCCGGGACGGCGGAAACAACCACAA CAACGAUACAGAGACAUUCAGGCCUGGCGGAGGCG ACAUGAGGGAUAACUGGAGAUCCGAGCUGUACAAG UACAAGGUGGUGAAGAUCGAGCCACUGGGAGUGGC UCCAACCAAGUGCAAGAGGAGAGUGGUGCAGUCUC ACAGCGGCAGCGGCGGCAGCGGCAGCGGAGGCCAC GCUGCUGUGGGAACAAUCGGAGCUAUGAGCCUGGG AUUUCUGGGAGCUGCUGGCAGCACCAUGGGAGCUG CUUCUAUCACACUGACCGUGCAGGCUAGGCUGCUG CUGUCCGGAAUCGUGCAGCAGCAGAACAACCUGCU GAGGGCUCCAGAGCCUCAGCAGCACCUGCUGCAGC UGACAGUGUGGGGCAUCAAGCAGCUGCAGGCCAGG GUGCUGGCUGUGGAGCACUACCUGAGGGACCAGCA GCUGCUGGGCAUCUGGGGAUGUAGCGGCAAGCUGA UCUGCUGUACCGCCGUGCCAUGGAACGCUUCCUGG UCUAACAAGACACUGGACAUGAUCUGGAACAACAU GACCUGGAUGGAGUGGGAGCGCGAGAUCGAUAACU ACACAGGCCUGAUCUACACCCUGAUCGAAGAAAGU CAGAAUCAGCAGGAAAAGAACGAACAGGAACUGCU GGAACUGGACGGUGGCGUCGAGAAUCUGUGGGUCA CCGUCUAUUAUGGAGUCCCCGUCUGGAAAGAGGCU ACUACUACACUGUUUUGUGCAAGCGAUGCCAAGGC CUACGACACAGAGGUGCACAACGUGUGGGCCACAC ACGAGUGCGUGCCAACCGAUCCAAACCCCCAGGAG GUGGUGCUGGAGAAUGUGACCGAGAAUUUCAACAU GUGGAAGAACAAUAUGGUGGAGCAGAUGCACGAGG ACAUCAUCGAGCUGUGGGAUCAGUCCCUGAAGCCU UGCGUGAAGCUGACACCACUGUGCGUGACACUGAA CUGUACCGACCUGAGGAAUGUGACCAACAUCAACA AUAGCUCCGAGGGCAUGAGAGGCGAGAUCAAGAAU UGUAGCUUCAACAUCACCACAUCCAUCCGGGACAA GGUGAAGAAGGAUUACGCCCUGUUUUAUCGCCUGG AUGUGGUGCCCAUCGACAAUGAUAACACCUCUUAC AGGCUGAUCAAUUGCAACACCAGCACAAUCACCCA GGCCUGUCCAAAGGUGUCCUUUGAGCCUAUCCCAA UCCACUAUUGCACACCCGCCGGCUUCGCCAUCCUG AAGUGUAAGGACAAGAAGUUUAACGGCACCGGCCC UUGCAAGAACGUGAGCACAGUGCAGUGUACCCACG GCAUCAGGCCAGUGGUGAGCACACAGCUGCUGCUG AACGGCUCCCUGGCCGAGGAGGAAGUGAUCAUCAG AUCUAGCAAUUUCACCGAUAAUGCCAAGAACAUCA UCGUGCAGCUGAAGGAGUCCGUGGAGAUCAACUGC ACAAGGCCCAACAAUAACACCGUGAAGUCUAUCCA CAUCGGCCCUGGCAGAGCCUUUUACUAUACCGGCG ACAUCAUCGGCGAUAUCCGGCAGGCCCACUGUAAC AUCAGCCGCACAAAGUGGAAUAACACCCUGAAUCA GAUCGCCACAAAGCUGAAGGAGCAGUUCGGCAAUA ACAAGACCAUCGUGUUUAACCAGUCCUCUGGCGGC GACCCCGAGAUCGUGAUGCACUCUUUCAAUUGCGG CGGCGAGUUCUUUUACUGUAACUCUACACAGCUGU UCAAUAGCACCUGGAACUUCAACGGCACAUGGAAU CUGACCCAGAGCAACGGCACCGAGGGCAAUGAUAC AAUCACCCUGCCUUGCCGGAUCAAGCAGAUCAUCA ACAUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCC CCUCCCAUCAGGGGACAGAUCAGGUGUAGCUCCAA UAUCACAGGCCUGAUCCUGACCCGGGACGGCGGAA AUAACCACAAUAACGAUACAGAGACAUUCAGGCCC GGCGGCGGCGACAUGAGGGAUAACUGGAGAUCCGA GCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCAC UGGGAGUGGCACCAACCAAGUGCAAGAGGAGAGUG GUGCAGUCUCACAGCGGCUCCGGCGGCUCUGGCAG CGGCGGCCACGCAGCAGUGGGAACAAUCGGAGCAA UGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCCACC AUGGGAGCAGCCUCUAUCACACUGACCGUGCAGGC AAGGCUGCUGCUGUCCGGCAUCGUGCAGCAGCAGA AUAACCUGCUGAGGGCACCAGAGCCUCAGCAGCAC CUGCUGCAGCUGACAGUGUGGGGCAUCAAGCAGCU GCAGGCCAGGGUGCUGGCAGUGGAGCACUAUCUGA GGGACCAGCAGCUGCUGGGCAUCUGGGGCUGUAGC GGCAAGCUGAUCUGCUGUACCGCCGUGCCCUGGAA CGCCUCCUGGUCUAAUAAGACACUGGACAUGAUCU GGAAUAACAUGACCUGGAUGGAGUGGGAGCGCGAG AUCGAUAACUACACAGGCCUGAUCUAUACCCUGAU UGAGGAGUCACAGAACCAGCAGGAAAAGAACGAAC AGGAACUGCUGGAACUGGAUUGAUAACUCGAG AD8_MD64_link14-RNA (SEQ ID NO: 260) GUGUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCU GGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGC UGGGAAUCUGGGGAUGCAGCGGCAAGCUGAUCUGC UGUACCGCCGUGCCAUGGAACGCCUCCUGGUCUAA UAAGACCCUGGACAUGAUCUGGAAUAACAUGACAU GGAUGGAGUGGGAGCGCGAGAUCGAUAACUACACC GGCCUGAUCUAUACACUGAUCGAGGAAUCACAGAA UCAGCAGGAGAAAAACGAACAGGAACUGCUGGAAC UGGAUUGAUAACUCGAGCAUUCUGUCGAAAACCUG UGGGUGACUGUCUAUUAUGGAGUGCCCGUGUGGAA GGAGGCCACCACAACCCUGUUCUGCGCCUCCGACG CCAAGGCCUACGAUACCGAGGUGCACAACGUGUGG GCCACCCACGAGUGCGUGCCUACAGACCCAAACCC CCAGGAGGUGGUGCUGGAGAAUGUGACAGAGAACU UCAACAUGUGGAAGAACAAUAUGGUGGAGCAGAUG CACGAGGACAUCAUCGAGCUGUGGGAUCAGAGCCU GAAGCCUUGCGUGAAGCUGACCCCACUGUGCGUGA CCCUGAAUUGUACAGACCUGCGGAAUGUGACAAAC AUCAACAAUAGCUCCGAGGGCAUGAGAGGCGAGAU CAAGAAUUGUAGCUUCAACAUCACAACCUCCAUCA GGGACAAGGUGAAGAAGGAUUACGCCCUGUUUUAU CGCCUGGAUGUGGUGCCCAUCGACAAUGAUAACAC CUCUUACCGGCUGAUCAAUUGCAACACAAGCACCA UCACACAGGCCUGUCCAAAGGUGUCCUUCGAGCCU AUCCCAAUCCACUAUUGCACCCCCGCCGGCUUCGC CAUCCUGAAGUGUAAGGACAAGAAGUUUAACGGCA CAGGCCCUUGCAAGAACGUGAGCACCGUGCAGUGU ACACACGGCAUCCGGCCAGUGGUGAGCACCCAGCU GCUGCUGAACGGCUCCCUGGCAGAGGAGGAAGUGA UCAUCAGAUCUAGCAAUUUCACAGAUAAUGCCAAG AACAUCAUCGUGCAGCUGAAGGAGUCCGUGGAGAU CAACUGCACCCGGCCCAACAAUAACACAGUGAAGU CUAUCCACAUCGGCCCUGGCAGAGCCUUUUACUAU ACCGGCGACAUCAUCGGCGAUAUCAGGCAGGCCCA CUGUAACAUCAGCCGCACCAAGUGGAAUAACACAC UGAAUCAGAUCGCCACCAAGCUGAAGGAGCAGUUC GGCAAUAACAAGACAAUCGUGUUUAACCAGUCCUC UGGCGGCGACCCAGAGAUCGUGAUGCACUCUUUUA AUUGCGGCGGCGAGUUCUUUUACUGUAACUCUACC CAGCUGUUCAAUAGCACAUGGAACUUCAACGGCAC CUGGAAUCUGACACAGAGCAACGGCACCGAGGGCA AUGAUACCAUCACACUGCCCUGCAGGAUCAAGCAG AUCAUCAACAUGUGGCAGGAAGUGGGCAAGGCCAU GUAUGCCCCUCCCAUCAGGGGCCAGAUCCGCUGUA GCUCCAAUAUCACCGGCCUGAUCCUGACAAGGGAC GGCGGAAAUAACCACAAUAACGAUACCGAGACAUU CCGCCCCGGCGGCGGCGACAUGAGGGAUAACUGGA GAUCCGAGCUGUACAAGUAUAAGGUGGUGAAGAUC GAGCCACUGGGAGUGGCACCAACCAAGUGCAAGAG GAGAGUGGUGCAGUCUCACAGCGGCUCCGGCGGCU CUGGCAGCGGCGGCCACGCCGCCGUGGGCACCAUC GGCGCCAUGAGCCUGGGCUUUCUGGGAGCAGCAGG CUCCACAAUGGGAGCAGCCUCUAUCACCCUGACAG UGCAGGCCAGGCUGCUGCUGUCCGGCAUCGUGCAG CAGCAGAAUAACCUGCUGAGGGCACCAGAGCCUCA GCAGCACCUGCUGCAGCUGACC 001428_MD39_link14_TS1-RNA (SEQ ID NO: 261) GGAUCCGCCACCAUGGACUGGACUUGGAUUCUGUU CCUGGUGGCAGCAGCAACUAGAGUGCAUUCCGUCG AAAACCUGUGGGUGACCGUGUAUUAUGGAGUGCCC GUGUGGAAGGAGGCCCGGACCACACUGUUCUGCGC CUCCGACGCCAAGGCCUACGAGACAGAGGUGCACA ACGUGUGGGCCACACACGCCUGCGUGCCUACCGAU CCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGAC CGAGAACUUUAAUAUGUGGAAGAACGACAUGGUGG AUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGCC CAGAGCCUGAAGCCUUGCGUGAAGCUGACCCCACU GUGCGUGACACUGGAGUGUACCCAGGUGAACGCCA CACAGGGCAAUACCACACAGGUGAACGUGACCCAA GUGAAUGGCGACGAGAUGAAGAACUGUUCCUUCAA UACCACAACCGAGAUCCGGGAUAAGAAGCAGAAGG CCUACGCCCUGUUUUAUAGACUGGACCUGGUGCCU CUGGAGCGGGAGAACAGAGGCGAUUCUAAUAGCGC CUCCAAGUAUAUCCUGAUCAACUGCAAUACAUCUG CCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGAU CCUAUCCCAAUCCACUACUGCACCCCAGCCGGCUA UGCCAUCCUGAAGUGUAACAACAAGACCUUCAACG GCACCGGCUCCUGCAACAACGUGAGCACAGUGCAG UGUACCCACGGCAUCAAGCCAGUGGUGAGCACCCA GCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAGA UCAUCAUCAGGUCCGAGAACCUGACAGACAAUGUG AAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGA GAUCGUGUGCACACGGCCAAACAAUAACACCGUGA AGUCUAUCAGAAUCGGCCCCGGCCAGACAUUCUAC UAUACCGGCGACAUCAUCGGCAAUAUCCGGGAGGC CCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGA UGCUGCGGAGAGUGAGCGAGAAGCUGGCCGAGCAC UUCCCCAAUAAGACAAUCAAGUUUACCAGCUCCUC UGGCGGCGAUCUGGAGAUCACAACCCACAGCUUCA ACUGCAGAGGCGAGUUCUUUUACUGUAACACCAGC GGCCUGUUUAAUUCCACAUACAUGCCCAACGGCAC CUAUAUGCCUAAUGGCACAAAUAACUCUAACAGCA CCAUCAUCCUGCCAUGCCGGAUCAAGCAGAUCAUC AAUAUGUGGCAGGAAGUGGGCAGAGCCAUGUAUGC CCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCA AUAUCACCGGCCUGCUGCUGGUGAGGGACGGCGGC AAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGG CGGCGACAUGAGGGAUAACUGGCGCUCCGAGCUGU ACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGA GUGGCACCAACCAGGUGCAAGAGGCGCGUGGUGGG CUCCCACUCUGGCAGCGGCGGCUCCGGCUCUGGCG GCCACGCAGCAGUGGGCCUGGGAGCCGUGAGCCUG GGCUUUCUGGGAGCAGCAGGCUCUACCAUGGGAGC AGCCAGCAUCACACUGACCGUGCAGGCAAGGCAGC UGCUGUCCGGCAUCGUGCAGCAGCAGUCUAACCUG CUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCA GGACACACACUGGGGCAUCAAGCAGCUGCAGACCC GCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAG CAGCUGCUGGGCAUCUGGGGCUGCUCUGGCAAGCU GAUCUGCUGUACAGCCGUGCCUUGGAACAGCUCCU GGAGCAAUAAGUCCCUGACAGACAUCUGGGAUAAU AUGACCUGGAUGCAGUGGGAUAGGGAGGUGAGCAA CUACACCGGCAUCAUCUAUCGCCUGCUGGAAGACU CACAGAAUCAGCAGGAAAGGAAUGAACAGGAUCUG CUGGCACUGGACGGGGGAGUCGAGAACCUCUGGGU CACCGUGUAUUAUGGAGUCCCCGUCUGGAAAGAAG CCCGAACCACCCUGUUUUGUGCCUCUGAUGCUAAA GCCUACGAGACAGAGGUGCACAACGUGUGGGCUAC ACACGCUUGCGUGCCAACCGACCCAAACCCCCAGG AGAUGGUGCUGGGCAACGUGACCGAGAACUUCAAC AUGUGGAAGAACGACAUGGUGGAUCAGAUGCACGA GGAUGUGAUCUCUCUGUGGGCCCAGAGCCUGAAGC CUUGCGUGAAGCUGACCCCACUGUGCGUGACACUG GAGUGUACCCAGGUGAACGCUACACAGGGCAACAC CACACAGGUGAACGUGACCCAGGUGAACGGAGACG AGAUGAAGAACUGUUCCUUCAACACCACAACCGAG AUCAGGGAUAAGAAGCAGAAGGCCUACGCUCUGUU UUACAGACUGGACCUGGUGCCACUGGAGAGGGAGA ACAGAGGCGAUUCUAACAGCGCCUCCAAGUACAUC CUGAUCAACUGCAACACAUCUGCCAUCACCCAGGC UUGUCCUAAGGUGAACUUCGACCCUAUCCCAAUCC ACUACUGCACACCAGCCGGCUACGCUAUCCUGAAG UGUAACAACAAGACCUUCAACGGAACCGGCUCCUG CAACAACGUGUCUACAGUGCAGUGUACCCACGGCA UCAAGCCCGUGGUGAGCACCCAGCUGCUGCUGAAC GGCAGCCUGGCUGAGGAGGAGAUCAUCAUCCGGUC CGAGAACCUGACAGACAACGUGAAGACCAUCAUCG UGCACCUGGAUCAGUCCGUGGAGAUCGUGUGCACA AGGCCAAACAACAACACCGUGAAGUCUAUCAGAAU CGGACCCGGCCAGACCUUCUACUACACCGGAGACA UCAUCGGCAACAUCAGGGAGGCCCACUGUAACAUC UCUGAGAAGAAGUGGCACGAGAUGCUGAGGAGAGU GAGCGAGAAGCUGGCUGAGCACUUCCCUAACAAGA CAAUCAAGUUUACCAGCUCCUCUGGCGGAGAUCUG GAGAUCACAACCCACAGCUUCAACUGCAGAGGAGA GUUCUUUUACUGUAACACCAGCGGCCUGUUUAACU CCACAUACAUGCCCAACGGAACCUACAUGCCUAAC GGCACAAACAACUCUAACAGCACCAUCAUCCUGCC CUGCAGGAUCAAGCAGAUCAUCAACAUGUGGCAGG AAGUGGGAAGAGCCAUGUACGCUCCCCCUAUCGCC GGCAACAUCACAUGUAACAGCAACAUCACCGGACU GCUGCUGGUGCGGGACGGCGGAAAGAACAACAACA CAGAGAUCUUCCGCCCUGGCGGAGGCGACAUGAGG GAUAACUGGCGCUCCGAGCUGUACAAGUACAAGGU GGUGGAGAUCAAGCCACUGGGAGUGGCUCCAACCA GGUGCAAGAGGAGGGUGGUGGGCAGCCACUCUGGC AGCGGAGGCUCCGGAUCUGGAGGCCACGCUGCUGU GGGACUGGGAGCCGUGAGCCUGGGAUUUCUGGGAG CUGCUGGAUCUACCAUGGGAGCUGCUAGCAUCACA CUGACCGUGCAGGCUAGGCAGCUGCUGUCCGGAAU CGUGCAGCAGCAGUCUAACCUGCUGCAGGCUCCCG AGCCUCAGCAGCACCUGCUGCAGGACACACACUGG GGCAUCAAGCAGCUGCAGACCCGCGUGCUGGCCAU CGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCA UCUGGGGAUGUUCUGGCAAGCUGAUCUGCUGUACA GCUGUGCCAUGGAACAGCUCCUGGAGCAACAAGUC CCUGACAGACAUCUGGGAUAACAUGACCUGGAUGC AGUGGGAUCGGGAGGUGAGCAACUACACCGGCAUC AUCUACCGCCUGCUGGAAGACUCACAGAAUCAGCA GGAACGGAAUGAACAGGACCUCCUCGCACUGGAUG GCGGAGUCGAAAACCUGUGGGUCACCGUCUACUAU GGAGUGCCAGUGUGGAAAGAGGCUAGGACUACCCU GUUCUGUGCCAGCGAUGCCAAAGCCUACGAGACAG AGGUGCACAACGUGUGGGCAACACACGCAUGCGUG CCAACCGACCCAAAUCCCCAGGAGAUGGUGCUGGG CAACGUGACCGAGAACUUCAAUAUGUGGAAGAACG ACAUGGUGGAUCAGAUGCACGAGGAUGUGAUCUCU CUGUGGGCCCAGAGCCUGAAGCCUUGCGUGAAGCU GACCCCACUGUGCGUGACACUGGAGUGUACCCAGG UGAACGCCACACAGGGCAAUACCACACAGGUGAAC GUGACCCAAGUGAAUGGCGACGAGAUGAAGAACUG UUCCUUCAAUACCACAACCGAGAUCAGGGAUAAGA AGCAGAAGGCCUACGCCCUGUUUUAUAGACUGGAC CUGGUGCCACUGGAGAGGGAGAACAGAGGCGAUUC UAAUAGCGCCUCCAAGUAUAUCCUGAUCAACUGCA AUACAUCUGCCAUCACCCAGGCCUGUCCUAAAGUG AAUUUCGACCCUAUCCCAAUCCACUACUGCACACC AGCCGGCUAUGCCAUCCUGAAGUGUAACAACAAGA CCUUCAACGGCACCGGCUCCUGCAACAACGUGAGC ACAGUGCAGUGUACCCACGGCAUCAAGCCCGUGGU GAGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAG AGGAGGAGAUCAUCAUCCGGUCCGAGAACCUGACA GACAAUGUGAAGACCAUCAUCGUGCACCUGGAUCA GUCCGUGGAGAUCGUGUGCACAAGGCCAAACAAUA ACACCGUGAAGUCUAUCAGAAUCGGCCCCGGCCAG ACCUUCUACUAUACCGGCGACAUCAUCGGCAAUAU CAGGGAGGCCCACUGUAACAUCUCUGAGAAGAAGU GGCACGAGAUGCUGAGGAGAGUGAGCGAGAAGCUG GCCGAGCACUUCCCUAAUAAGACAAUCAAGUUUAC CAGCUCCUCUGGCGGCGAUCUGGAGAUCACAACCC ACAGCUUCAACUGCAGAGGCGAGUUCUUUUACUGU AACACCAGCGGCCUGUUUAAUUCCACAUACAUGCC CAACGGCACCUAUAUGCCUAAUGGCACAAAUAACU CUAACAGCACCAUCAUCCUGCCCUGCAGGAUCAAG CAGAUCAUCAAUAUGUGGCAGGAAGUGGGCAGAGC CAUGUAUGCCCCUCCCAUCGCCGGCAACAUCACAU GUAACAGCAAUAUCACCGGCCUGCUGCUGGUGCGG GACGGCGGCAAGAAUAACAAUACAGAGAUCUUCCG CCCCGGCGGCGGCGACAUGAGGGAUAACUGGCGCU CCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAG CCACUGGGAGUGGCACCAACCAGGUGCAAGAGGCG CGUGGUGGGCUCCCACUCUGGCAGCGGCGGCUCCG GCUCUGGCGGCCACGCAGCAGUGGGCCUGGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCUAC CAUGGGAGCAGCCAGCAUCACACUGACCGUGCAGG CAAGGCAGCUGCUGUCCGGCAUCGUGCAGCAGCAG UCUAACCUGCUGCAGGCACCAGAGCCUCAGCAGCA CCUGCUGCAGGACACACACUGGGGCAUCAAGCAGC UGCAGACCCGCGUGCUGGCCAUCGAGCACUACCUG AAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUC UGGCAAGCUGAUCUGCUGUACAGCCGUGCCAUGGA ACAGCUCCUGGAGCAAUAAGUCCCUGACAGACAUC UGGGAUAAUAUGACCUGGAUGCAGUGGGAUCGGGA GGUGAGCAACUACACCGGCAUCAUCUAUCGCCUGC UGGAGGACUCACAGAAUCAGCAGGAGCGGAACGAA CAGGAUCUGCUGGCACUGGAUUGAUAACUCGAG 001428_MD39_link14-RNA (SEQ ID NO: 262) GGAUCCGCCACCAUGGACUGGACUUGGAUUCUGUU CCUGGUGGCAGCAGCAACUAGAGUGCAUUCCGUCG AAAACCUGUGGGUGACCGUGUAUUAUGGAGUGCCC GUGUGGAAGGAGGCCCGGACCACACUGUUCUGCGC CUCCGACGCCAAGGCCUACGAGACAGAGGUGCACA ACGUGUGGGCCACACACGCCUGCGUGCCUACCGAU CCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGAC CGAGAACUUUAAUAUGUGGAAGAACGACAUGGUGG AUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGCC CAGAGCCUGAAGCCUUGCGUGAAGCUGACCCCACU GUGCGUGACACUGGAGUGUACCCAGGUGAACGCCA CACAGGGCAAUACCACACAGGUGAACGUGACCCAA GUGAAUGGCGACGAGAUGAAGAACUGUUCCUUCAA UACCACAACCGAGAUCCGGGAUAAGAAGCAGAAGG CCUACGCCCUGUUUUAUAGACUGGACCUGGUGCCU CUGGAGCGGGAGAACAGAGGCGAUUCUAAUAGCGC CUCCAAGUAUAUCCUGAUCAACUGCAAUACAUCUG CCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGAU CCUAUCCCAAUCCACUACUGCACCCCAGCCGGCUA UGCCAUCCUGAAGUGUAACAACAAGACCUUCAACG GCACCGGCUCCUGCAACAACGUGAGCACAGUGCAG UGUACCCACGGCAUCAAGCCAGUGGUGAGCACCCA GCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAGA UCAUCAUCAGGUCCGAGAACCUGACAGACAAUGUG AAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGA GAUCGUGUGCACACGGCCAAACAAUAACACCGUGA AGUCUAUCAGAAUCGGCCCCGGCCAGACAUUCUAC UAUACCGGCGACAUCAUCGGCAAUAUCCGGGAGGC CCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGA UGCUGCGGAGAGUGAGCGAGAAGCUGGCCGAGCAC UUCCCCAAUAAGACAAUCAAGUUUACCAGCUCCUC UGGCGGCGAUCUGGAGAUCACAACCCACAGCUUCA ACUGCAGAGGCGAGUUCUUUUACUGUAACACCAGC GGCCUGUUUAAUUCCACAUACAUGCCCAACGGCAC CUAUAUGCCUAAUGGCACAAAUAACUCUAACAGCA CCAUCAUCCUGCCAUGCCGGAUCAAGCAGAUCAUC AAUAUGUGGCAGGAAGUGGGCAGAGCCAUGUAUGC CCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCA AUAUCACCGGCCUGCUGCUGGUGAGGGACGGCGGC AAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGG CGGCGACAUGAGGGAUAACUGGCGCUCCGAGCUGU ACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGA GUGGCACCAACCAGGUGCAAGAGGCGCGUGGUGGG CUCCCACUCUGGCAGCGGCGGCUCCGGCUCUGGCG GCCACGCAGCAGUGGGCCUGGGAGCCGUGAGCCUG GGCUUUCUGGGAGCAGCAGGCUCUACCAUGGGAGC AGCCAGCAUCACACUGACCGUGCAGGCAAGGCAGC UGCUGUCCGGCAUCGUGCAGCAGCAGUCUAACCUG CUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCA GGACACACACUGGGGCAUCAAGCAGCUGCAGACCC GCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAG CAGCUGCUGGGCAUCUGGGGCUGCUCUGGCAAGCU GAUCUGCUGUACAGCCGUGCCUUGGAACAGCUCCU GGAGCAAUAAGUCCCUGACAGACAUCUGGGAUAAU AUGACCUGGAUGCAGUGGGAUAGGGAGGUGAGCAA CUACACCGGCAUCAUCUAUCGCCUGCUGGAAGACU CACAGAAUCAGCAGGAAAGGAAUGAACAGGAUCUG CUGGCACUGGACUGAUAACUCGAG BG505_SOSIP_MD39_link14 RNA GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUC CGGCGGCUCUGGCAGCGGCGGCCACGCCGCAGUGG GCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCA GCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCU GACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCG UGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAG CCCCAGCAGCACCUGCUGAAGGACACCCACUGGGG CAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGG AGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUC UGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAA UGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACC UGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAG UGGGAUAAGGAGAUCUCCAACUACACACAGAUCAU CUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGG AAAAGAAUGAACAGGAUCUGCUGGCACUGGAUUGA UAACUCGAG BG505_SOSIP_MD39_CPG9.2_ circular permutation)-RNA (SEQ ID NO: 263) GGAUCCGCCACCAUGGAUUGGACUUGGAUUCUGUU CCUGGUCGCAGCAGCCACACGAGUGCAUAGCGGGG GAAAUAGUAGCGGCAGCCUGGGGUUCCUGGGAGCA GCAGGCUCCACCAUGGGAGCAGCAUCUAUGACCCU GACAGUGCAGGCCAGGAAUCUGCUGUCUGGCAUCG UGCAGCAGCAGAGCAACCUGCUGAGAGCCCCAGAG CCCCAGCAGCACCUGCUGAAGGACACCCACUGGGG CAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAGUGG AGCACUACCUGCGCGAUCAGCAGCUGCUGGGAAUC UGGGGAUGCAGCGGCAAGCUGAUCUGCUGUACAAA UGUGCCUUGGAACAGCUCCUGGUCCAAUAGGAACC UGUCUGAGAUCUGGGACAAUAUGACCUGGCUGAAC UGGUCUAAGGAGAUCAGCAAUUACACACAGAUCAU CUAUGGCCUGCUGGAGGAGAGCCAGAAUCAGAACG AGUCCAAUGAGCAGGAUCUGGGCGGCAACGGCAGC GGCGGCGGCAGCGGCUCCGGCGGCAACGGCUCUAG CGGCCUGUGGGUGACCGUGUACUAUGGCGUGCCCG UGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCC UCCGAUGCCAAGGCCUAUGAGACAGAGAAGCACAA CGUGUGGGCAACCCACGCAUGCGUGCCAACAGACC CUAACCCACAGGAGAUCCACCUGGAGAAUGUGACC GAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGA GCAGAUGCACGAGGACAUCAUCAGCCUGUGGGAUC AGUCCCUGAAGCCUUGCGUGAAGCUGACCCCACUG UGCGUGACACUGCAGUGUACCAACGUGACAAACAA UAUCACCGACGAUAUGAGGGGCGAGCUGAAGAAUU GUUCUUUCAACAUGACCACAGAGCUGAGGGACAAG AAGCAGAAAGUGUACAGCCUGUUUUAUAGACUGGA UGUGGUGCAGAUCAAUGAGAACCAGGGCAAUAGGA GCAACAAUUCCAACAAGGAGUACAGACUGAUCAAU UGCAACACCAGCGCCAUCACACAGGCCUGUCCAAA GGUGUCCUUCGAGCCCAUCCCUAUCCACUAUUGCG CACCAGCAGGAUUCGCAAUCCUGAAGUGUAAGGAU AAGAAGUUUAACGGAACCGGACCAUGCCCAUCUGU GAGCACCGUGCAGUGUACACACGGCAUCAAGCCAG UGGUGUCCACACAGCUGCUGCUGAAUGGCUCUCUG GCCGAGGAGGAAGUGAUCAUCCGGAGCGAGAACAU CACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUGA ACACACCCGUGCAGAUCAAUUGCACCCGGCCUAAC AAUAACACAGUGAAGUCCAUCAGGAUCGGACCAGG ACAGGCCUUUUACUAUACCGGCGACAUCAUCGGCG AUAUCCGCCAGGCCCACUGUAACGUGAGCAAGGCC ACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCA GCUGAGGAAGCACUUCGGCAAUAACACCAUCAUCA GAUUUGCACAGUCCUCUGGCGGCGACCUGGAGGUG ACCACACACUCCUUCAACUGCGGCGGCGAGUUCUU UUACUGUAACACAUCUGGCCUGUUUAAUAGCACCU GGAUCUCUAACACAAGCGUGCAGGGCUCCAAUUCU ACCGGCUCCAACGAUUCUAUCACACUGCCCUGCCG GAUCAAGCAGAUCAUCAACAUGUGGCAGAGGAUCG GACAGGCAAUGUACGCCCCUCCCAUCCAGGGCGUG AUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCCU GACACGCGACGGCGGCAGCACCAACUCCACCACAG AGACAUUCAGACCCGGCGGCGGCGACAUGAGGGAU AACUGGAGAUCCGAGCUGUAUAAGUAUAAAGUCGU GAAGAUUGAGCCACUGGGCGUCGCACCAACAAGAU GUAAUAGAAGCUGAUAACUCGAG BG505_MD39_GRSF (Glycan)-RNA (SEQ ID NO: 264) GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACG GCGCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCU UUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCC UCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCU GAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGA GAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGAC ACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGU GCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGC UGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUC UGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUC UAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGA CCUGGCUGAACUGGAGCAAGGAGAUCUCCAACUAC ACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCA GAAUCAGCAGGAAAAGAAUAACCAGAGCCUGCUGG CACUGGAUUGAUAACUCGAG BG505_SOSIP_MD39-RNA (SEQ ID NO: 265) GGAUCCGCCACCAUGGACUGGACAUGGAUUCUGUU CCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCG AAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCC GUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACA ACGUGUGGGCAACCCACGCAUGCGUGCCUACAGAC CCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGAC AGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGG AGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAU CAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCU GUGCGUGACACUGCAGUGUACCAACGUGACAAACA AUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAU UGUAGCUUCAACAUGACCACAGAGCUGAGGGACAA GAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGG AUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGG UCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAA UUGCAACACCUCCGCCAUCACACAGGCCUGUCCUA AGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGC GCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGA UAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCU GUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCU GGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACA UCACCAACAAUGCCAAGAAUAUCCUGGUGCAGCUG AACACACCAGUGCAGAUCAAUUGCACCCGGCCCAA CAAUAACACAGUGAAGUCUAUCCGCAUCGGCCCAG GCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGC GAUAUCAGACAGGCCCACUGUAAUGUGAGCAAGGC CACCUGGAACGAGACACUGGGCAAGGUGGUGAAGC AGCUGAGGAAGCACUUCGGCAAUAACACCAUCAUC AGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGU GACCACACACUCCUUCAAUUGCGGCGGCGAGUUCU UUUACUGUAACACAAGCGGCCUGUUUAAUUCCACC UGGAUCUCCAACACAUCUGUGCAGGGCAGCAAUUC CACCGGCAGCAACGAUUCCAUCACACUGCCAUGCC GGAUCAAGCAGAUCAUCAACAUGUGGCAGCGCAUC GGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGU GAUCAGAUGCGUGAGCAAUAUCACCGGCCUGAUCC UGACACGCGACGGCGGCUCUACCAACAGCACCACA GAGACAUUCCGGCCCGGCGGCGGCGACAUGAGGGA UAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGG UGAAGAUCGAGCCUCUGGGAGUGGCACCAACCAGG UGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACG GCGCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCU UUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCC UCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCU GAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGA GAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGAC ACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGU GCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGC UGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUC UGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUC UAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGA CCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUAC ACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCA GAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGG CACUGGAUUGAUAACUCGAG

B. Polypeptide Sequences

Disclosed are the polypeptide sequences encoded by the disclosed nucleic acid sequences. Thus, disclosed are the polypeptide sequences encoded by the leader sequence, self-assembling polypeptide encoded by a nucleotide sequence, polypeptide sequences encoded by the linker, and viral antigens encoded by a nucleotide sequence. The disclosure also relates to cells expressing one or more polypeptides disclosed in the application.

In some embodiments, the polypeptide encoded by the leader sequence can be the IgE amino acid sequence MDWTWILFLVAAATRVHS encoded by SEQ ID NO:1-6.

MQIYEGKLTAEGLRFGIVASRANHALVDRLVEGAIDAIVRH GGREEDITLVRVCGSWEIPVAAGELARKEDIDAVIAIGVLC RGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQ AIEAAGTCHGNKGWEAALCAIEMANLFKSLRGGS encoded by SEQ ID NO:.

In some embodiments, the polypeptide sequences encoded by a portion of the expressible nucleic acid sequence can be GGSGGSGGSGGG.

Also disclosed is the polypeptide comprising the IgE leader sequence and a gp120 variant viral antigen comprising the sequence MDWTWILFLVAAATRVHSDTITLPCRPAPPPHCSSNITGLILTRQGGYSNDNTVIFRPS GGDWRDIARCQIAGTVVSTQLFLNGSLAEEEVVIRSEDWRDNAKSICVQLNTSVEIN CTGAGHCNISRAKWNNTLKQIASKLREQYGNKTIIFKPSSGGDPEFVNHSFNCGGEFF YCDSTQLFNSTWFNST. In some embodiments, the composition comprises at least one expressible nucleic acid sequence disclosed herein or any nucleic acid sequence at least about 70%, 75%, 80%, 85%, 86%, 87% 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 59 SEQ ID NO: 60, SEQ ID NO: 62 SEQ ID NO: 63, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 90, SEQ ID NO: 91 or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, the composition comprises at least one expressible nucleic acid sequence disclosed herein or any nucleic acid sequence at least about 70%, 75%, 80%, 85%, 86%, 87% 88%, 89%, 90%, 91%, 92%. 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 106 SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 130, SEQ ID NO: 131 or a pharmaceutically acceptable salt of any of the foregoing.

In some embodiments, the composition, nucleic acid molecule or nucleic acid sequence of the disclosure relates to any a plasmid comprising any nucleic acid or combination of nucleic acid sequences chosen from those that are at least about 70%, 75%, 80%, 85%, 86%, 87% 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to those nucleic acid sequences disclosed from SEQ ID NO: 154 through SEQ ID NO: 238. In some embodiments, the composition, nucleic acid molecule or nucleic acid sequence of the disclosure relates to any a plasmid comprising any nucleic acid or combination of nucleic acid sequences that encode an amino acid sequence that comprises at least about 70%, 75%, 80%, 85%, 86%, 87% 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence within or between from SEQ ID NO: 154 through SEQ ID NO: 238.

C. Pharmaceutical Compositions

Disclosed are pharmaceutical compositions comprising any one or more of the disclosed compositions and a pharmaceutically acceptable carrier.

In some embodiments, any of the disclosed compositions is from about 1 to about 30 micrograms of the disclosed DNA and/or RNA vaccine. For example, any of the disclosed compositions can be from about 1 to about 5 micrograms the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain from about 5 nanograms to about 800 micrograms of the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain about 25 to about 250 micrograms, from about 100 to about 200 micrograms, from about 1 nanogram to 100 milligrams; from about 1 microgram to about 10 milligrams; from about 0.1 microgram to about 10 milligrams; from about 1 milligram to about 2 milligrams, from about 5 nanograms to about 1000 micrograms, from about 10 nanograms to about 800 micrograms, from about 0.1 to about 500 micrograms, from about 1 to about 350 micrograms, from about 25 to about 250 micrograms, from about 100 to about 200 micrograms of the DNA and/or RNA vaccine or plasmid thereof. The pharmaceutical compositions can comprise from about 5 nanograms to about 10 mg of the disclosed DNA and/or RNA vaccine. In some embodiments, pharmaceutical compositions according to the present invention comprise from about 25 nanograms to about 5 mg of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain from about 50 nanograms to about 1 mg of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about from about 0.1 to about 500 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain from about 1 to about 350 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain from about 5 to about 250 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain from about 10 to about 200 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain from about 15 to about 150 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about 20 to about 100 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about 25 to about 75 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about 30 to about 50 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about 35 to about 40 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions contain about 100 to about 200 micrograms the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions comprise about 10 micrograms to about 100 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions comprise about 20 micrograms to about 80 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions comprise about 25 micrograms to about 60 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions comprise about 30 nanograms to about 50 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions comprise about 35 nanograms to about 45 micrograms of the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain about 0.1 to about 500 micrograms of the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain about 1 to about 350 micrograms of the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain about 1 to about 250 micrograms of the disclosed DNA and/or RNA vaccine. In some preferred embodiments, the pharmaceutical compositions contain about 2 to about 200 micrograms the disclosed DNA and/or RNA vaccine.

In some embodiments, pharmaceutical compositions according to the present invention comprise at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 nanograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical compositions can comprise at least about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, 440, 445, 450, 455, 460, 465, 470, 475, 480, 485, 490, 495, 500, 605, 610, 615, 620, 625, 630, 635, 640, 645, 650, 655, 660, 665, 670, 675, 680, 685, 690, 695, 700, 705, 710, 715, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765, 770, 775, 780, 785, 790, 795, 800, 805, 810, 815, 820, 825, 830,835, 840,845, 850, 855, 860, 865,870, 875, 880, 885, 890, 895, 900, 905, 910, 915, 920, 925, 930, 935, 940, 945, 950, 955, 960, 965, 970, 975, 980, 985, 990, 995 or 1000 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical composition can comprise at least 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 mg or more of the disclosed DNA and/or RNA vaccine.

In other embodiments, the pharmaceutical composition can comprise up to and including about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 nanograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical composition can comprise up to and including about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300, 305, 310, 315, 320, 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, 440, 445, 450, 455, 460, 465, 470, 475, 480, 485, 490, 495, 500, 605, 610, 615, 620, 625, 630, 635, 640, 645, 650, 655, 660, 665, 670, 675, 680, 685, 690, 695, 700, 705, 710, 715, 720, 725, 730, 735, 740, 745, 750, 755, 760, 765, 770, 775, 780, 785, 790, 795, 800, 805, 810, 815, 820, 825, 830, 835, 840, 845, 850, 855, 860, 865, 870, 875, 880, 885, 890, 895, 900, 905, 910, 915, 920, 925, 930, 935, 940, 945, 950, 955, 960, 965, 970, 975, 980, 985, 990, 995, or 1000 micrograms of the disclosed DNA and/or RNA vaccine. In some embodiments, the pharmaceutical composition can comprise up to and including about 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or about 10 mg of the disclosed DNA and/or RNA vaccine. The pharmaceutical composition can further comprise other agents for formulation purposes according to the mode of administration to be used. In cases where pharmaceutical compositions are injectable pharmaceutical compositions, they are sterile, pyrogen free and particulate free. An isotonic formulation is preferably used. Generally, additives for isotonicity can include sodium chloride, dextrose, mannitol, sorbitol and lactose. In some cases, isotonic solutions such as phosphate buffered saline are preferred. Stabilizers include gelatin and albumin. In some embodiments, a vasoconstriction agent is added to the formulation.

The vaccine can further comprise a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient can be functional molecules as vehicles, adjuvants, carriers, or diluents. The pharmaceutically acceptable excipient can be a transfection facilitating agent, which can include surface active agents, such as immune-stimulating complexes (ISCOMS), Freunds incomplete adjuvant, LPS analog including monophosphoryl lipid A, muramyl peptides, quinone analogs, vesicles such as squalene and squalene, hyaluronic acid, lipids, liposomes, calcium ions, viral proteins, polyanions, polycations, or other known transfection facilitating agents. In some embodiments, the vaccine is a composition comprising a plasmid DNA molecule, RNA molecule or DNA/RNA hybrid molecule encoding an expressible nucleic acid sequence, the expressible nucleic acid sequence comprising a first nucleic acid encoding a self-assembling nanoparticle polypeptide and a second nucleic acid sequence comprising one, two, or three or more contiguous or non-contiguous retroviral envelope antigens, optionally encoding a leader sequence disclosed herein.

The transfection facilitating agent is a polyanion, polycation, including poly-L-glutamate (LGS), or lipid. The transfection facilitating agent is poly-L-glutamate, and more preferably, the poly-L-glutamate is present in the vaccine at a concentration less than 6 mg/ml. The transfection facilitating agent can also include surface active agents such as immune-stimulating complexes (ISCOMS), Freunds incomplete adjuvant, LPS analog including monophosphoryl lipid A, muramyl peptides, quinone analogs and vesicles such as squalene and squalene, and hyaluronic acid can also be used administered in conjunction with the genetic construct. In some embodiments, the DNA vector vaccines can also include a transfection facilitating agent such as lipids, liposomes, including lecithin liposomes or other liposomes known in the art, as a DNA-liposome mixture (see for example WO9324640), calcium ions, viral proteins, polyanions, polycations, or nanoparticles, or other known transfection facilitating agents. Preferably, the transfection facilitating agent is a polyanion, polycation, including poly-L-glutamate (LGS), or lipid. Concentration of the transfection agent in the vaccine is less than 4 mg/ml, less than 2 mg/ml, less than 1 mg/ml, less than 0.750 mg/ml, less than 0.500 mg/ml, less than 0.250 mg/ml, less than 0.100 mg/ml, less than 0.050 mg/ml, or less than 0.010 mg/ml.

The pharmaceutically acceptable excipient can be an adjuvant. The adjuvant can be other genes that are expressed in alternative plasmid or are deneurological systemed as proteins in combination with the plasmid above in the vaccine. The adjuvant can be selected from the group consisting of α-interferon (IFN-α), β-interferon (IFN-β), γ-interferon, platelet derived growth factor (PDGF), TNFα, TNFβ, GM-CSF, epidermal growth factor (EGF), cutaneous T cell-attracting chemokine (CTACK), epithelial thymus-expressed chemokine (TECK), mucosae-associated epithelial chemokine (MEC), IL-12, IL-15, MHC, CD80, CD86 including IL-15 having the signal sequence deleted and optionally including the signal peptide from IgE. The adjuvant can be IL-12, IL-15, IL-28, CTACK, TECK, platelet derived growth factor (PDGF), TNFα, TNFβ, GM-CSF, epidermal growth factor (EGF), IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, or a combination thereof. In an exemplary embodiment, the adjuvant is IL-12.

Other genes which can be useful adjuvants include those encoding: MCP-1, MIP-1a, MIP-1p, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, p150.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, mutant forms of IL-18, CD40, CD40L, vascular growth factor, fibroblast growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Fit, Apo-1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, Caspase ICE, Fos, c-jun, Sp-1, Ap-1, Ap-2, p38, p65Rel, MyD88, IRAK, TRAF6, IkB, Inactive NIK, SAP K, SAP-1, JNK, interferon response genes, NFkB, Bax, TRAIL, TRAILrec, TRAILrecDRC5, TRAIL-R3, TRAIL-R4, RANK, RANK LIGAND, Ox40, Ox40 LIGAND, NKG2D, MICA, MICB, NKG2A, NKG2B, NKG2C, NKG2E, NKG2F, TAP1, TAP2 and functional fragments thereof or a combination thereof.

In some embodiments adjuvant may be one or more proteins and/or nucleic acid molecules that encode proteins selected from the group consisting of: CCL-20, IL-12, IL-15, IL-28, CTACK, TECK, MEC or RANTES. Examples of IL-12 constructs and sequences are disclosed in PCT application No. PCT/US1997/019502 (published as WO98/017799) and corresponding U.S. application Ser. No. 08/956,865, and U.S. Provisional Application No. 61/569,600 filed Dec. 12, 2011, which are each incorporated herein by reference in their entireties. Examples of IL-15 constructs and sequences are disclosed in PCT application No. PCT/US04/18962 (published as WO2005/000235) and corresponding U.S. application Ser. No. 10/560,650, and in PCT application No. PCT/US07/00886 (published as WO2007/087178) and corresponding U.S. application Ser. No. 12/160,766, and in PCT Application Serial No. PCT/US10/048827 (published as WO2011/032179), which are each incorporated herein by reference in their entireties. Examples of IL-28 constructs and sequences are disclosed in PCT application no. PCT/US09/039648 (published as WO2009/124309) and corresponding U.S. application Ser. No. 12/936,192, which are each incorporated herein by reference in their entireties. Examples of RANTES and other constructs and sequences are disclosed in PCT application No. PCT/US 1999/004332 (published as WO99/043839) and corresponding U.S. Application Serial No. and 09/622,452, which are each incorporated herein by reference in their entireties. Other examples of RANTES constructs and sequences are disclosed in PCT Application No. PCT/US Serial No. 11/024098 (published as WO2011/097640), which is incorporated herein by reference. Examples of RANTES and other constructs and sequences are disclosed in PCT Application No. PCT/US 1999/004332 and corresponding U.S. application Ser. No. 09/622,452, which are each incorporated herein by reference. Other examples of RANTES constructs and sequences are disclosed in PCT application No. PCT/US11/024098 (published as WO2011/097640), which is incorporated herein by reference in its entirety. Examples of chemokines CTACK, TECK and MEC constructs and sequences are disclosed in PCT Application No. PCT/US2005/042231 (published as WO2007/050095) and corresponding U.S. application Ser. No. 11/719,646, which are each incorporated herein by reference in their entireties. Examples of OX40 and other immunomodulators are disclosed in U.S. application Ser. No. 10/560,653, which is incorporated herein by reference in its entirety. Examples of DR5 and other immunomodulators are disclosed in U.S. application Ser. No. 09/622,452, which is incorporated herein by reference in its entirety.

The pharmaceutical composition may be formulated according to the mode of administration to be used. An injectable vaccine pharmaceutical composition may be sterile, pyrogen free and particulate free. An isotonic formulation or solution may be used. Additives for isotonicity may include sodium chloride, dextrose, mannitol, sorbitol, and lactose. The vaccine may comprise a vasoconstriction agent. The isotonic solutions may include phosphate buffered saline. Vaccine may further comprise stabilizers including gelatin and albumin. The stabilizing may allow the formulation to be stable at room or ambient temperature for extended periods of time such as LGS or polycations or polyanions to the vaccine formulation.

The vaccine can be a DNA vaccine. DNA vaccines are disclosed in U.S. Pat. Nos. 5,593,972, 5,739,118, 5,817,637, 5,830,876, 5,962,428, 5,981,505, 5,580,859, 5,703,055, and 5,676,594, which are incorporated herein fully by reference. The DNA vaccine can further comprise elements or reagents that inhibit it from integrating into the chromosome. Examples of attenuated live vaccines, those using recombinant vectors to foreign antigens, subunit vaccines and glycoprotein vaccines are described in U.S. Pat. Nos. 4,510,245; 4,797,368; 4,722,848; 4,790,987; 4,920,209; 5,017,487; 5,077,044; 5,110,587; 5,112,749; 5,174,993; 5,223,424; 5,225,336; 5,240,703; 5,242,829; 5,294,441; 5,294,548; 5,310,668; 5,387,744; 5,389,368; 5,424,065; 5,451,499; 5,453,364; 5,462,734; 5,470,734; 5,474,935; 5,482,713; 5,591,439; 5,643,579; 5,650,309; 5,698,202; 5,955,088; 6,034,298; 6,042,836; 6,156,319 and 6,589,529, which are each incorporated herein by reference in their entireties.

The genetic construct can also be part of a genome of a recombinant viral vector, including recombinant adenovirus, recombinant adenovirus associated virus and recombinant vaccinia. The genetic construct can be part of the genetic material in attenuated live microorganisms or recombinant microbial vectors which live in cells

D. Methods

Disclosed are methods of vaccinating a subject comprising administering a therapeutically effective amount of any of the disclosed pharmaceutical compositions to the subject. Disclosed are methods of inducing an immune response in a subject comprising administering to the subject any of the disclosed pharmaceutical compositions.

Disclosed are methods of neutralizing one or a plurality of viruses in a subject comprising administering to the subject any of the disclosed pharmaceutical compositions.

Disclosed are methods of stimulating a therapeutically effective antigen-specific immune response against a virus in a mammal infected with the virus comprising administering any of the disclosed pharmaceutical compositions. Disclosed are methods of inducing expression of a self-assembling vaccine in a subject comprising administering any of the disclosed pharmaceutical compositions. Also disclosed are methods of treating a subject having a viral infection or susceptible to becoming infected with a virus comprising administering to the subject any of the disclosed pharmaceutical compositions.

In some embodiments, the administering can be accomplished by oral administration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration, topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof. In some embodiments, the above modes of action are accomplished by injection of the pharmaceutical compositions disclosed herein. In some embodiments, the therapeutically effective dose can be from about 1 to about 30 micrograms of expressible nucleic acid sequence. In some embodiments, the therapeutically effective dose can be from about 0.001 micrograms of composition per kilogram of subject to about 0.050 micrograms per kilogram of subject.

In some embodiments, any of the disclosed methods can be free of activating any mannose-binding lectin or complement process.

In some embodiments, the subject can be a human. In some embodiments, the subject is diagnosed with or suspected of having a viral infection. For example, the subject can be diagnosed with or suspected of having an HIV-1 infection.

In some embodiments of the methods of inducing an immune response, the immune response can be an antigen-specific immune response. For example, the antigen-specific immune response can be an HIV-1 antigen immune response.

In some embodiments, any of the disclosed methods can further comprise administering to the subject a pharmaceutical composition comprising one or more pharmaceutically active agents, such as antiviral drugs, among many others. In some embodiments, the one or more pharmaceutically active agents include other antiretroviral medications used to inhibit HIV, for example nucleoside analog reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Among the available drugs that may be used as a pharmaceutically active agent are zidovudine or AZT (or Retrovir®), didanosine or DDI (or Videx®), stavudine or D4T (or Zerit®), lamivudine or 3TC (or EpivirR), zalcitabine or DDC (or Hivid®), abacavir succinate (or Ziagen”), tenofovir disoproxil fumarate salt (or Viread®), emtricitabine (or Emtriva®), Combivir® (contains 3TC and AZT). Trizivir® (contains abacavir, 3TC and AZT); three non-nucleoside reverse transcriptase inhibitors: nevirapine (or Viramune®), delavirdine (or Rescriptor®) and efavirenz (or Sustiva®), eight peptidomimetic protease inhibitors or approved formulations: saquinavir (or InviraseR or Fortovase”), indinavir (or Crixivan®), ritonavir (or Norvir®), nelfinavir (or Viracept”), amprenavir (or Agenerase®), atazanavir (Reyataz), fosamprenavir (or Lexiva), Kaletra® (contains lopinavir and ritonavir), and one fusion inhibitor enfuvirtide (or T-20 or FuzeonR).

In some embodiments, the methods are free of administering any polypeptide directly to the subject. In some embodiments, methods of inducing an immune response can include inducing a humoral or cellular immune response. A humoral immune response can include induction of CD4+ cells and antibody production. A cellular immune response can include activating CD8+ cells and cytotoxic activity. In one aspect, the present disclosure features a method of inducing an immune response in a subject, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of any of the nucleic acid molecules of any one of the aspects or embodiments herein, or any one of the pharmaceutical compositions of any one of the aspects and embodiments herein. In one aspect, the present disclosure features a method of inducing a CD8+ T cell immune response in a subject, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of any of the nucleic acid molecules of any one of the aspects or embodiments herein, or any one of the pharmaceutical compositions of any one of the aspects and embodiments herein.

In one aspect, the present disclosure features a method of enhancing an immune response in a subject, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of any of the nucleic acid molecules of any one of the aspects or embodiments herein, or any one of the pharmaceutical compositions of any one of the aspects and embodiments herein.

In one aspect, the present disclosure features a method of enhancing a CD8+ T cell immune response in a subject against a virus, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of any of the nucleic acid molecules of any one of the aspects or embodiments herein, or any one of the pharmaceutical compositions of any one of the aspects and embodiments herein. In another embodiment, the subject has previously been treated, and not responded to anti-viral therapy. In some embodiments, the nucleic acid molecule and/or expressible sequence is administered to the subject by electroporation.

The nucleic acid sequence or vaccine may be administered by different routes including orally, parenterally, sublingually, transdermally, rectally, transmucosally, topically, via inhalation, via buccal administration, intrapleurally, intravenous, intraarterial, intraperitoneal, subcutaneous, intramuscular, intranasal intrathecal, and intraarticular or combinations thereof. For veterinary use, the composition may be administered as a suitably acceptable formulation in accordance with normal veterinary practice. The veterinarian can readily determine the dosing regimen and route of administration that is most appropriate for a particular animal. The vaccine may be administered by traditional syringes, needleless injection devices, “microprojectile bombardment gone guns”, or other physical methods such as electroporation (“EP”), “hydrodynamic method”, or ultrasound.

The plasmid comprising one, two three or more expressible nucleic acid sequences may be delivered to the mammal by several well-known technologies including DNA injection (also referred to as DNA vaccination) with and without in vivo electroporation, liposome mediated, nanoparticle facilitated, recombinant vectors such as recombinant adenovirus, recombinant adenovirus associated virus and recombinant vaccinia. The consensus antigen may be delivered via DNA injection and, optionally, with in vivo electroporation. In some embodiments, the vaccine or pharmaceutical composition can be administered by electroporation. Administration of the vaccine via electroporation of the plasmids of the vaccine may be accomplished using electroporation devices that can be configured to deliver to a desired tissue of a mammal a pulse of energy effective to cause reversible pores to form in cell membranes, and preferable the pulse of energy is a constant current similar to a preset current input by a user. The electroporation device may comprise an electroporation component and an electrode assembly or handle assembly. The electroporation component may include and incorporate one or more of the various elements of the electroporation devices, including: controller, current waveform generator, impedance tester, waveform logger, input element, status reporting element, communication port, memory component, power source, and power switch. The electroporation can be accomplished using an in vivo electroporation device, for example CELLECTRA® EP system (Inovio Pharmaceuticals, Inc., Blue Bell, Pa.) or Elgen electroporator (Inovio Pharmaceuticals, Inc.) to facilitate transfection of cells by the plasmid.

The electroporation component may function as one element of the electroporation devices, and the other elements are separate elements (or components) in communication with the electroporation component. The electroporation component may function as more than one element of the electroporation devices, which may be in communication with still other elements of the electroporation devices separate from the electroporation component. The elements of the electroporation devices existing as parts of one electromechanical or mechanical device may not limited as the elements can function as one device or as separate elements in communication with one another. The electroporation component may be capable of delivering the pulse of energy that produces the constant current in the desired tissue, and includes a feedback mechanism. The electrode assembly may include an electrode array having a plurality of electrodes in a spatial arrangement, wherein the electrode assembly receives the pulse of energy from the electroporation component and delivers same to the desired tissue through the electrodes. At least one of the plurality of electrodes is neutral during delivery of the pulse of energy and measures impedance in the desired tissue and communicates the impedance to the electroporation component. The feedback mechanism may receive the measured impedance and can adjust the pulse of energy delivered by the electroporation component to maintain the constant current.

A plurality of electrodes may deliver the pulse of energy in a decentralized pattern. The plurality of electrodes may deliver the pulse of energy in the decentralized pattern through the control of the electrodes under a programmed sequence, and the programmed sequence is input by a user to the electroporation component. The programmed sequence may comprise a plurality of pulses delivered in sequence, wherein each pulse of the plurality of pulses is delivered by at least two active electrodes with one neutral electrode that measures impedance, and wherein a subsequent pulse of the plurality of pulses is delivered by a different one of at least two active electrodes with one neutral electrode that measures impedance. The feedback mechanism may be performed by either hardware or software. The feedback mechanism may be performed by an analog closed-loop circuit. The feedback occurs every 50 μs, 20 s, 10 μs or 1 μs, but is preferably a real-time feedback or instantaneous (i.e., substantially instantaneous as determined by available techniques for determining response time). The neutral electrode may measure the impedance in the desired tissue and communicates the impedance to the feedback mechanism, and the feedback mechanism responds to the impedance and adjusts the pulse of energy to maintain the constant current at a value similar to the preset current. The feedback mechanism may maintain the constant current continuously and instantaneously during the delivery of the pulse of energy.

Examples of electroporation devices and electroporation methods that may facilitate delivery of the DNA vaccines of the present invention, include those described in U.S. Pat. No. 7,245,963 by Draghia-Akli, et al., U.S. Patent Pub. 2005/0052630 submitted by Smith, et al., the contents of which are hereby incorporated by reference in their entirety. Other electroporation devices and electroporation methods that may be used for facilitating delivery of the DNA vaccines include those provided in co-pending and co-owned U.S. patent application Ser. No. 11/874,072, filed Oct. 17, 2007, which claims the benefit under 35 USC 119(e) to U.S. Provisional Applications Nos. 60/852,149, filed Oct. 17, 2006, and 60/978,982, filed Oct. 10, 2007, all of which are hereby incorporated in their entirety.

U.S. Pat. No. 7,245,963 by Draghia-Akli, et al. describes modular electrode systems and their use for facilitating the introduction of a biomolecule into cells of a selected tissue in a body or plant. The modular electrode systems may comprise a plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. An operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert them into the selected tissue in a body or plant. The biomolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes. The applied constant-current electrical pulse facilitates the introduction of the biomolecule into the cell between the plurality of electrodes. The entire content of U.S. Pat. No. 7,245,963 is hereby incorporated by reference in its entirety.

U.S. Patent Pub. 2005/0052630 submitted by Smith, et al. describes an electroporation device which may be used to effectively facilitate the introduction of a biomolecule into cells of a selected tissue in a body or plant. The electroporation device comprises an electro-kinetic device (“EKD device”) whose operation is specified by software or firmware. The EKD device produces a series of programmable constant-current pulse patterns between electrodes in an array based on user control and input of the pulse parameters, and allows the storage and acquisition of current waveform data. The electroporation device also comprises a replaceable electrode disk having an array of needle electrodes, a central injection channel for an injection needle, and a removable guide disk. The entire content of U.S. Patent Pub. 2005/0052630 is hereby incorporated by reference. The electrode arrays and methods described in U.S. Pat. No. 7,245,963 and U.S. Patent Pub. 2005/0052630 may be adapted for deep penetration into not only tissues such as muscle, but also other tissues or organs. Because of the configuration of the electrode array, the injection needle (to deliver the biomolecule of choice) is also inserted completely into the target organ, and the injection is administered perpendicular to the target issue, in the area that is pre-delineated by the electrodes The electrodes described in U.S. Pat. No. 7,245,963 and U.S. Patent Pub. 2005/005263 are preferably 20 mm long and 21 gauge.

Additionally, contemplated in some embodiments that incorporate electroporation devices and uses thereof, there are electroporation devices that are those described in the following patents: U.S. Pat. No. 5,273,525 issued Dec. 28, 1993, U.S. Pat. No. 6,110,161 issued Aug. 29, 2000, U.S. Pat. No. 6,261,281 issued Jul. 17, 2001, and U.S. Pat. No. 6,958,060 issued Oct. 25, 2005, and U.S. Pat. No. 6,939,862 issued Sep. 6, 2005. Furthermore, patents covering subject matter provided in U.S. Pat. No. 6,697,669 issued Feb. 24, 2004, which concerns delivery of DNA using any of a variety of devices, and U.S. Pat. No. 7,328,064 issued Feb. 5, 2008, drawn to a method of injecting DNA are contemplated herein. The above-patents are incorporated by reference in their entirety.

Methods of preparing the nucleic acid sequences are disclosed. In some embodiments, plasmid sequences with one or more multiple cloning sites may be purchased from commercially available vendors and the expressible nucleic acid sequences disclosed herein may be ligated into the plasmids after a digestion with a known restriction enzyme needed to cute the plasmid DNA. In some embodiments, the nucleic acid molecule comprises at least one expressible nucleic acid sequence encoding a first, second and third monomeric HIV-1 ENV polypeptide or variant thereof. In some embodiments, at least one of the first, second or third monomeric HIV-1 ENV polypeptides comprises one or a plurality of mouse codons. In another alternative embodiment, membrane-based purification methods disclosed herein offer reduced cost, high binding capacity, and high flow rates, resulting in a superior purification process. The purification process is further demonstrated to produce plasmid products substantially free of genomic DNA, RNA, protein, and endotoxin.

In some embodiments, all of the described aspects of the current disclosure are advantageously combined to provide an integrated process for preparing substantially purified cellular components of interest from cells in bioreactors. Again, the cells are most preferably plasmid-containing cells, and the cellular components of interest are most preferably plasmids. The substantially purified plasmids are suitable for various uses, including, but not limited to, gene therapy, plasmid-mediated therapy, as DNA vaccines for human, veterinary, or agricultural use, or for any other application that requires large quantities of purified plasmid. In this aspect, all of the advantages described for individual aspects of the present invention accrue to the complete, integrated process, providing a highly advantageous method that is rapid, scalable, and inexpensive. Enzymes and other animal-derived or biologically sourced products are avoided, as are carcinogenic, mutagenic, or otherwise toxic substances. Potentially flammable, explosive, or toxic organic solvents are similarly avoided.

One aspect of the present disclosure is an apparatus for isolating plasmid DNA from a suspension of cells having both plasmid DNA and genomic DNA. An embodiment of the apparatus comprises a first tank and second tank in fluid communication with a mixer. The first tank is used for holding the suspension cells and the second tank is used for holding a lysis solution. The suspension of cells from the first tank and the lysis solution from the second tank are both allowed to flow into the mixer forming a lysate mixture or lysate fluid. The mixer comprises a high shear, low residence-time mixing device with a residence time of equal to or less than about 1 second. In a preferred embodiment, the mixing device comprises a flow through, rotor/stator mixer or emulsifier having linear flow rates from about 0.1 L/min to about 20 L/min. The lysate-mixture flows from the mixer into a holding coil for a period of time sufficient to lyse the cells and forming a cell lysate suspension, wherein the lysate-mixture has resident time in the holding coil in a range of about 2-8 minutes with a continuous linear flow rate. The cell lysate suspension is then allowed to flow into a bubble-mixer chamber for precipitation of cellular components from the plasmid DNA. In the bubble mixer chamber, the cell lysate suspension and a precipitation solution or a neutralization solution from a third tank are mixed together using gas bubbles, which forms a mixed gas suspension comprising a precipitate and an unclarified lysate or plasmid containing fluid. The precipitate of the mixed gas suspension is less dense than the plasmid containing fluid, which facilitates the separation of the precipitate from the plasmid containing fluid. The precipitate is removed from the mixed gas suspension to give a clarified lysate having the plasmid DNA, and the precipitate having cellular debris and genomic DNA.

In some embodiments, the bubble mixer-chamber comprises a closed vertical column with a top, a bottom, a first, and a second side with a vent proximal to the top of the column. A first inlet port of the bubble mixer-chamber is on the first side proximal to the bottom of the column and in fluid communication with the holding coil. A second inlet port of the bubble mixer-chamber is proximal to the bottom on a second side opposite of the first inlet port and in fluid communication with a third tank, wherein the third tank is used for holding a precipitation or a neutralization solution. A third inlet port of the bubble mixer-chamber is proximal to the bottom of the column and about in the middle of the first and second inlets and is in fluid communication with a gas source the third inlet entering the bubble-mixer-chamber. A preferred embodiment utilizes a sintered sparger inside the closed vertical column of the third inlet port. The outlet port exiting the bubble mixing chamber is proximal to the top of the closed vertical column. The outlet port is in fluid communication with a fourth tank, wherein the mixed gas suspension containing the plasmid DNA is allowed to flow from the bubble-mixer-chamber into the fourth tank. The fourth tank is used for separating the precipitate of the mixed gas suspension having a plasmid containing fluid, and can also include an impeller mixer sufficient to provide uniform mixing of fluid without disturbing the precipitate. A fifth tank is used for a holding the clarified lysate or clarified plasmid containing fluid. The clarified lysate is then filtered at least once. A first filter has a particle size limit of about 5-10 m and the second filter has a cut of about 0.2 m. Although gravity, pressure, vacuum, or a mixture thereof can be used for transporting: suspension of cells; lysis solutions; precipitation solutions; neutralization solutions; or mixed gas suspensions from any of the tanks to mixers, holding coils or different tanks, pumps are utilized in a preferred embodiments. In a more preferred embodiment, at least one pump having a linear flow rate from about 0.1 to about 1 ft/second is used.

In another specific embodiment, a Y-connector having a having a first bifurcated branch, a second bifurcated branch and an exit branch is used to contact the cell suspension and the lysis solutions before they enter the high shear, low residence-time mixing device. The first tank holding the cell suspension is in fluid communication with the first bifurcated branch of the Y-connector through the first pump and the second tank holding the lysis solution is in fluid communication with the second bifurcated branch of the Y-connector through the second pump. The high shear, low residence-time mixing device is in fluid communication with an exit branch of the Y-connector, wherein the first and second pumps provide a linear flow rate of about 0.1 to about 2 ft/second for a contacted fluid exiting the Y-connector.

Another specific aspect of the present invention is a method of substantially separating plasmid DNA and genomic DNA from a bacterial cell lysate. The method comprises: delivering a cell lysate into a chamber; delivering a precipitation fluid or a neutralization fluid into the chamber; mixing the cell lysate and the precipitation fluid or a neutralization fluid in the chamber with gas bubbles forming a gas mixed suspension, wherein the gas mixed suspension comprises the plasmid DNA in a fluid portion (i.e. an unclarified lysate) and the genomic DNA is in a precipitate that is less dense than the fluid portion; floating the precipitate on top of the fluid portion; removing the fluid portion from the precipitate forming a clarified lysate, whereby the plasmid DNA in the clarified lysate is substantially separated from genomic DNA in the precipitate. In preferred embodiments: the chamber is the bubble mixing chamber as described above; the lysing solution comprises an alkali, an acid, a detergent, an organic solvent, an enzyme, a chaotrope, or a denaturant; the precipitation fluid or the neutralization fluid comprises potassium acetate, ammonium acetate, or a mixture thereof; and the gas bubbles comprise compressed air or an inert gas. Additionally, the decanted-fluid portion containing the plasmid DNA is preferably further purified with one or more purification steps selected from a group consisting of ion exchange, hydrophobic interaction, size exclusion, reverse phase purification, endotoxin depletion, affinity purification, adsorption to silica, glass, or polymeric materials, expanded bed chromatography, mixed mode chromatography, displacement chromatography, hydroxyapatite purification, selective precipitation, aqueous two-phase purification, DNA condensation, thiophilic purification, ion-pair purification, metal chelate purification, filtration through nitrocellulose, or ultrafiltration.

In some embodiments, a method for isolating a plasmid DNA from cells comprising: mixing a suspension of cells having the plasmid DNA and genomic DNA with a lysis solution in a high-shear-low-residence-time-mixing-device for a first period of time forming a cell lysate fluid; incubating the cell lysate fluid for a second period of time in a holding coil forming a cell lysate suspension; delivering the cell lysate suspension into a chamber; delivering a precipitation/neutralization fluid into the chamber; mixing the cell lysate suspension and the a precipitation/neutralization fluid in the chamber with gas bubbles forming a gas mixed suspension, wherein the gas mixed suspension comprises an unclarified lysate containing the plasmid DNA and a precipitate containing the genomic DNA, wherein the precipitate is less dense than the unclarified lysate; floating the precipitate on top of the unclarified lysate; removing the precipitate from the unclarified lysate forming a clarified lysate, whereby the plasmid DNA is substantially separated from genomic DNA; precipitating the plasmid DNA from the clarified lysate forming a precipitated plasmid DNA; and resuspending the precipitated plasmid DNA in an aqueous solution.

The disclosure also relates to a method of producing a polypeptide of interest in a mammalian cell, the method comprising contacting the cell with a composition comprising a nanoparticle or the nucleic acid sequences that are RNA in the attached document. In some embodiments, the therapeutic and/or prophylactic agent is an mRNA, and wherein the mRNA encodes the polypeptide of interest, whereby the mRNA is capable of being translated in the cell to produce the polypeptide of interest. Compositions comprising RNA nucleic acid sequences of the disclosure can be delivered via lipid-containing nanoparticles and/or modification of the RNA nucleic acid sequence encoding the one or more viral polypeptides.

In some embodiments, the composition includes at least one RNA polynucleotide having an open reading frame encoding at least one HIV antigenic polypeptide having at least one modification, at least one 5′ terminal cap, and is formulated within a lipid nanoparticle.

In some embodiments, a 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp. In some embodiments, at least one chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine, and 2′-O-methyl uridine.

In some embodiments, a lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol, and a non-cationic lipid. In some embodiments, a cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. In some embodiments, a cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), (12Z,15Z)—N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine (L608), and N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine (L530).

In some embodiments, HIV RNA (e.g. mRNA) vaccines are formulated in a lipid nanoparticle. In some embodiments, HIV RNA (e.g. mRNA) vaccines are formulated in a lipid-polycation complex, referred to as a cationic lipid nanoparticle. The formation of the lipid nanoparticle may be accomplished by methods known in the art and/or as described in U.S. Publication No. 20120178702, herein incorporated by reference in its entirety. As a non-limiting example, the polycation may include a cationic peptide or a polypeptide such as, but not limited to, polylysine, polyorithine and/or polyarginine and the cationic peptides described in International Publication No. WO2012013326 or U.S. Publication No. US20130142818; each of which is herein incorporated by reference in its entirety. In some embodiments, HIV RNA (e.g. mRNA) vaccines are formulated in a lipid nanoparticle that includes a non-cationic lipid such as, but not limited to, cholesterol or dioleoyl phosphatidylethanolamine (DOPE).

A lipid nanoparticle formulation may be influenced by, but not limited to, the selection of the cationic lipid component, the degree of cationic lipid saturation, the nature of the PEGylation, ratio of all components, and biophysical parameters such as size. In one example by Semple et al. (Nature Biotech. 2010 28:172-176; herein incorporated by reference in its entirety), the lipid nanoparticle formulation is composed of 57.1% cationic lipid, 7.1% dipalmitoylphosphatidylcholine, 34.3% cholesterol, and 1.4% PEG-c-DMA. As another example, changing the composition of the cationic lipid was shown to more effectively deliver siRNA to various antigen presenting cells (Basha et al. Mol Ther. 2011 19:2186-2200; herein incorporated by reference in its entirety).

In some embodiments, lipid nanoparticle formulations may comprise 35% to 45% cationic lipid, 40% to 50% cationic lipid, 50% to 60% cationic lipid and/or 55% to 65% cationic lipid. In some embodiments, the ratio of lipid to RNA (e.g., mRNA) in lipid nanoparticles may be 5:1 to 20:1, 10:1 to 25:1, 15:1 to 30:1, and/or at least 30:1.

In some embodiments, the ratio of PEG in the lipid nanoparticle formulations may be increased or decreased and/or the carbon chain length of the PEG lipid may be modified from C14 to C18 to alter the pharmacokinetics and/or biodistribution of the lipid nanoparticle formulations. As a non-limiting example, lipid nanoparticle formulations may contain 0.5% to 3.0%, 1.0% to 3.5%, 1.5% to 4.0%, 2.0% to 4.5%, 2.5% to 5.0%, and/or 3.0% to 6.0% of the lipid molar ratio of PEG-c-DOMG (R-3-[(co-methoxy-poly(ethyleneglycol)2000) carbamoyl)]-1,2-dimyristyloxypropyl-3-amine) (also referred to herein as PEG-DOMG) as compared to the cationic lipid, DSPC, and cholesterol. In some embodiments, the PEG-c-DOMG may be replaced with a PEG lipid such as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol, methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol) and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol). The cationic lipid may be selected from any lipid known in the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA. C12-200, and DLin-KC2-DMA.

In some embodiments, a HIV RNA (e.g., mRNA) vaccine formulation is a nanoparticle that comprises at least one lipid. The lipid may be selected from, but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, (12Z,15Z)—N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine (L608), N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]heptadecan-8-amine (L530), PEGylated lipids, and amino alcohol lipids.

In some embodiments, a lipid nanoparticle formulation includes 25% to 75% on a molar basis of a cationic lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), e.g., 35% to 65%, 45% to 65%, 60%, 57.5%, 50% or 40% on a molar basis.

In some embodiments, a lipid nanoparticle formulation includes 0.5% to 15% on a molar basis of the neutral lipid, e.g., 3% to 12%, 5% to 10% or 15%, 10%, or 7.5% on a molar basis. Examples of neutral lipids include, without limitation, DSPC, POPC, DPPC, DOPE, and SM. In some embodiments, the formulation includes 5% to 50% on a molar basis of the sterol (e.g., 15% to 45%, 20% to 40%, 40%, 38.5%, 35%, or 31% on a molar basis. A non-limiting example of a sterol is cholesterol. In some embodiments, a lipid nanoparticle formulation includes 0.5% to 20% on a molar basis of the PEG or PEG-modified lipid (e.g., 0.5% to 10%, 0.5% to 5%, 1.5%, 0.5%, 1.5%, 3.5%, or 5% on a molar basis. In some embodiments, a PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of 2,000 Da. In some embodiments, a PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of less than 2,000, for example around 1,500 Da, around 1,000 Da, or around 500 Da. Non-limiting examples of PEG-modified lipids include PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C14 or C14-PEG), and PEG-cDMA (further discussed in Reyes et al. J. Controlled Release, 107, 276-287 (2005) the content of which is herein incorporated by reference in its entirety).

In some embodiments, lipid nanoparticle formulations include 25-75% of a cationic lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 0.5-15% of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or PEG-modified lipid on a molar basis.

In some embodiments, lipid nanoparticle formulations include 35-65% of a cationic lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 3-12% of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.

In some embodiments, lipid nanoparticle formulations include 45-65% of a cationic lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 5-10% of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.

In some embodiments, lipid nanoparticle formulations include 60% of a cationic lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 7.5% of the neutral lipid, 31% of the sterol, and 1.5% of the PEG or PEG-modified lipid on a molar basis.

Some embodiments of the present disclosure provide a HIV vaccine that includes at least one ribonucleic acid (RNA) polynucleotide having an open reading frame encoding at least one HIV antigenic polypeptide, wherein at least about 80% of the uracil in the open reading frame have a chemical modification, optionally wherein the HIV vaccine is formulated in a lipid nanoparticle. In some embodiments, the RNA vaccine pharmaceutical compositions may be formulated in liposomes such as, but not limited to, DiLa2 liposomes (Marina Biotech, Bothell, Wash.), SMARTICLES® (Marina Biotech, Bothell, Wash.), neutral DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes (e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer Biology & Therapy 2006 5(12)1708-1713); herein incorporated by reference in its entirety) and hyaluronan-coated liposomes (Quiet Therapeutics, Israel). In some embodiments, the RNA vaccines may be formulated in a lyophilized gel-phase liposomal composition as described in U.S. Publication No. US2012060293, herein incorporated by reference in its entirety.

The nanoparticle formulations may comprise a phosphate conjugate. The phosphate conjugate may increase in vivo circulation times and/or increase the targeted delivery of the nanoparticle. Phosphate conjugates for use with the present invention may be made by the methods described in International Publication No. WO2013033438 or U.S. Publication No. US20130196948, the content of each of which is herein incorporated by reference in its entirety. As a non-limiting example, the phosphate conjugates may include a compound of any one of the formulas described in International Publication No. WO2013033438, herein incorporated by reference in its entirety. In particular, the present invention relates to a pharmaceutical composition comprising nanoparticles which comprise RNA encoding at least one antigen, wherein:

(i) the number of positive charges in the nanoparticles does not exceed the number of negative charges in the nanoparticles and/or

(ii) the nanoparticles have a neutral or net negative charge and/or

(iii) the charge ratio of positive charges to negative charges in the nanoparticles is 1.4:1 or less and/or

(iv) the zeta potential of the nanoparticles is 0 or less.

In some embodiments, the nanoparticles described herein are colloidally stable for at least 2 hours in the sense that no aggregation, precipitation or increase of size and polydispersity index by more than 30% as measured by dynamic light scattering takes place. In some embodiments, the charge ratio of positive charges to negative charges in the nanoparticles is between 1.4:1 and 1:8, preferably between 1.2:1 and 1:4, e.g. between 1:1 and 1:3 such as between 1:1.2 and 1:2, 1:1.2 and 1:1.8, 1:1.3 and 1:1.7, in particular between 1:1.4 and 1:1.6, such as about 1:1.5. In some embodiments, the zeta potential of the nanoparticles is −5 or less, −10 or less, −15 or less, −20 or less or −25 or less. In various embodiments, the zeta potential of the nanoparticles is −35 or higher, −30 or higher or −25 or higher. In some embodiments, the nanoparticles have a zeta potential from 0 mV to −50 mV, preferably 0 mV to −40 mV or −10 mV to −30 mV.

In some embodiments pharmaceutical compositions of the disclosure comprise a nanoparticle or a liposome that encapsulates a DNA, RNA or DNA/RNA hybrid comprising at least one expressible nucleic acid sequence. Liposomes are microscopic lipidic vesicles often having one or more bilayers of a vesicle-forming lipid, such as a phospholipid, and are capable of encapsulating a drug. Different types of liposomes may be employed in the context of the present invention, including, without being limited thereto, multilamellar vesicles (MLV), small unilamellar vesicles (SUV), large unilamellar vesicles (LUV), sterically stabilized liposomes (SSL), multivesicular vesicles (MV), and large multivesicular vesicles (LMV) as well as other bilayered forms known in the art. The size and lamellarity of the liposome will depend on the manner of preparation and the selection of the type of vesicles to be used will depend on the preferred mode of administration. There are several other forms of supramolecular organization in which lipids may be present in an aqueous medium, comprising lamellar phases, hexagonal and inverse hexagonal phases, cubic phases, micelles, reverse micelles composed of monolayers. These phases may also be obtained in the combination with DNA or RNA, and the interaction with RNA and DNA may substantially affect the phase state. The described phases may be present in the nanoparticulate RNA formulations of the present invention.

For formation of RNA lipoplexes from RNA and liposomes, any suitable method of forming liposomes can be used so long as it provides the envisaged RNA lipoplexes. Liposomes may be formed using standard methods such as the reverse evaporation method (REV), the ethanol injection method, the dehydration-rehydration method (DRV), sonication or other suitable methods.

After liposome formation, the liposomes can be sized to obtain a population of liposomes having a substantially homogeneous size range.

Bilayer-forming lipids have typically two hydrocarbon chains, particularly acyl chains, and a head group, either polar or nonpolar. Bilayer-forming lipids are either composed of naturally-occurring lipids or of synthetic origin, including the phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatide acid, phosphatidylinositol, and sphingomyelin, where the two hydrocarbon chains are typically between about 14-22 carbon atoms in length, and have varying degrees of unsaturation. Other suitable lipids for use in the composition of the present invention include glycolipids and sterols such as cholesterol and its various analogs which can also be used in the liposomes.

Cationic lipids typically have a lipophilic moiety, such as a sterol, an acyl or diacyl chain, and have an overall net positive charge. The head group of the lipid typically carries the positive charge. The cationic lipid preferably has a positive charge of 1 to 10 valences, more preferably a positive charge of 1 to 3 valences, and more preferably a positive charge of 1 valence. Examples of cationic lipids include, but are not limited to 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA); dimethyldioctadecylammonium (DDAB); 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP); 1,2-dioleoyl-3-dimethylammonium-propane (DODAP); 1,2-diacyloxy-3-dimethylammonium propanes; 1,2-dialkyloxy-3-dimethylammonium propanes; dioctadecyldimethyl ammonium chloride (DODAC), 1,2-dimyristoyloxypropyl-1,3-dimethylhydroxyethyl ammonium (DMRIE), and 2,3-dioleoyloxy-N-[2(spermine carboxamide)ethyl]-N,N-dimethyl-1-propanamium trifluoroacetate (DOSPA). Preferred are DOTMA, DOTAP, DODAC, and DOSPA. Most preferred is DOTMA.

In addition, the nanoparticles described herein preferably further include a neutral lipid in view of structural stability and the like. The neutral lipid can be appropriately selected in view of the delivery efficiency of the RNA-lipid complex. Examples of neutral lipids include, but are not limited to, 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), diacylphosphatidyl choline, diacylphosphatidyl ethanol amine, ceramide, sphingoemyelin, cephalin, sterol, and cerebroside. Preferred is DOPE and/or DOPC. Most preferred is DOPE. In the case where a cationic liposome includes both a cationic lipid and a neutral lipid, the molar ratio of the cationic lipid to the neutral lipid can be appropriately determined in view of stability of the liposome and the like.

According to one embodiment, the nanoparticles described herein may comprise phospholipids. The phospholipids may be a glycerophospholipid. Examples of glycerophospholipid include, without being limited thereto, three types of lipids: (i) zwitterionic phospholipids, which include, for example, phosphatidylcholine (PC), egg yolk phosphatidylcholine, soybean-derived PC in natural, partially hydrogenated or fully hydrogenated form, dimyristoyl phosphatidylcholine (DMPC) sphingomyelin (SM); (ii) negatively charged phospholipids: which include, for example, phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), phosphatidylglycerol (PG) dipalmipoyl PG, dimyristoyl phosphatidylglycerol (DMPG); synthetic derivatives in which the conjugate renders a zwitterionic phospholipid negatively charged such is the case of methoxy-polyethylene,glycol-distearoyl phosphatidylethanolamine (mPEG-DSPE); and (iii) cationic phospholipids, which include, for example, phosphatidylcholine or sphingomyelin of which the phosphomonoester was O-methylated to form the cationic lipids.

Association of RNA to the lipid carrier can occur, for example, by the RNA filling interstitial spaces of the carrier, such that the carrier physically entraps the RNA, or by covalent, ionic, or hydrogen bonding, or by means of adsorption by non-specific bonds. Whatever the mode of association, the RNA must retain its therapeutic, i.e. antigen-encoding, properties.

In some embodiments, the nanoparticles comprise at least one lipid. In some embodiments, the nanoparticles comprise at least one cationic lipid. The cationic lipid can be monocationic or polycationic. Any cationic amphiphilic molecule, e.g., a molecule which comprises at least one hydrophilic and lipophilic moiety is a cationic lipid within the meaning of the present invention. In some embodiments, the positive charges are contributed by the at least one cationic lipid and the negative charges are contributed by the RNA. In some embodiments, the nanoparticles comprises at least one helper lipid. The helper lipid may be a neutral or an anionic lipid. The helper lipid may be a natural lipid, such as a phospholipid or an analogue of a natural lipid, or a fully synthetic lipid, or lipid-like molecule, with no similarities with natural lipids. In some embodiments, the cationic lipid and/or the helper lipid is a bilayer forming lipid.

In some embodiments, the at least one cationic lipid comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) or analogs or derivatives thereof and/or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or analogs or derivatives thereof. In some embodiments, the at least one helper lipid comprises 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE) or analogs or derivatives thereof, cholesterol (Chol) or analogs or derivatives thereof and/or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or analogs or derivatives thereof. In some embodiments, the molar ratio of the at least one cationic lipid to the at least one helper lipid is from 10:0 to 3:7, preferably 9:1 to 3:7, 4:1 to 1:2, 4:1 to 2:3, 7:3 to 1:1, or 2:1 to 1:1, preferably about 1:1. In some embodiments, in this ratio, the molar amount of the cationic lipid results from the molar amount of the cationic lipid multiplied by the number of positive charges in the cationic lipid. In various embodiments, the lipids are not functionalized such as functionalized by mannose, histidine and/or imidazole, the nanoparticles do not comprise a targeting ligand such as mannose functionalized lipids and/or the nanoparticles do not comprise one or more of the following: pH dependent compounds, cationic polymers such as polymers containing histidine and/or polylysine, wherein the polymers may optionally be PEGylated and/or histidylated, or divalent ions such as Ca 2+.

In various embodiments, the RNA nanoparticles may comprise peptides, preferentially with a molecular weight of up to 2500 Da.

In the nanoparticles described herein the lipid may form a complex with and/or may encapsulate the RNA. In some embodiments, the nanoparticles comprise a lipoplex or liposome. In some embodiments, the lipid is comprised in a vesicle encapsulating said RNA. The vesicle may be a multilamellar vesicle, an unilamellar vesicle, or a mixture thereof. The vesicle may be a liposome. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 10:0 to 1:9, preferably 8:2 to 3:7, and more preferably of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, more preferably 1.6:2 to 1:2, even more preferably 1.4:2 to 1.1:2 and even more preferably about 1.2:2.

In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and Cholesterol in a molar ratio of 10:0 to 1:9, preferably 8:2 to 3:7, and more preferably of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, more preferably 1.6:2 to 1:2, even more preferably 1.4:2 to 1.1:2 and even more preferably about 1.2:2. In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 10:0 to 1:9, preferably 8:2 to 3:7, and more preferably of 7:3 to 5:5 and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.8:2 to 0.8:2, more preferably 1.6:2 to 1:2, even more preferably 1.4:2 to 1.1:2 and even more preferably about 1.2:2. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and DOPE in a molar ratio of 2:1 to 1:2, preferably 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles are lipoplexes comprising DOTMA and cholesterol in a molar ratio of 2:1 to 1:2, preferably 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTMA to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles are lipoplexes comprising DOTAP and DOPE in a molar ratio of 2:1 to 1:2, preferably 2:1 to 1:1, and wherein the charge ratio of positive charges in DOTAP to negative charges in the RNA is 1.4:1 or less. In some embodiments, the nanoparticles have an average diameter in the range of from about 50 nm to about 1000 nm, preferably from about 50 nm to about 400 nm, preferably about 100 nm to about 300 nm such as about 150 nm to about 200 nm. In some embodiments, the nanoparticles have a diameter in the range of about 200 to about 700 nm, about 200 to about 600 nm, preferably about 250 to about 550 nm, in particular about 300 to about 500 nm or about 200 to about 400 nm.

In some embodiments, the polydispersity index of the nanoparticles described herein as measured by dynamic light scattering is 0.5 or less, preferably 0.4 or less or even more preferably 0.3 or less. In some embodiments, the nanoparticles described herein are obtainable by one or more of the following: (i) incubation of liposomes in an aqueous phase with the RNA in an aqueous phase, (ii) incubation of the lipid dissolved in an organic, water miscible solvent, such as ethanol, with the RNA in aqueous solution, (iii) reverse phase evaporation technique, (iv) freezing and thawing of the product, (v) dehydration and rehydration of the product, (vi) lyophilization and rehydration of the of the product, or (vii) spray drying and rehydration of the product.

The nanoparticle formulation may comprise a polymer conjugate. The polymer conjugate may be a water-soluble conjugate. The polymer conjugate may have a structure as described in U.S. Publication No. 20130059360, the content of which is herein incorporated by reference in its entirety. In some aspects, polymer conjugates with the polynucleotides of the present invention may be made using the methods and/or segmented polymeric reagents described in U.S. Publication No. 20130072709, herein incorporated by reference in its entirety. In other aspects, the polymer conjugate may have pendant side groups comprising ring moieties such as, but not limited to, the polymer conjugates described in U.S. Publication No. US20130196948, the contents of which is herein incorporated by reference in its entirety.

The nanoparticle formulations may comprise a conjugate to enhance the delivery of nanoparticles of the present invention in a subject. Further, the conjugate may inhibit phagocytic clearance of the nanoparticles in a subject. In some aspects, the conjugate may be a “self” peptide designed from the human membrane protein CD47 (e.g., the “self” particles described by Rodriguez et al. (Science 2013, 339, 971-975), herein incorporated by reference in its entirety). As shown by Rodriguez et al., the self peptides delayed macrophage-mediated clearance of nanoparticles which enhanced delivery of the nanoparticles. In other aspects, the conjugate may be the membrane protein CD47 (e.g., see Rodriguez et al. Science 2013, 339, 971-975, herein incorporated by reference in its entirety). Rodriguez et al. showed that, similarly to “self” peptides, CD47 can increase the circulating particle ratio in a subject as compared to scrambled peptides and PEG coated nanoparticles.

In some embodiments, 100% of the uracil in the open reading frame have a chemical modification. In some embodiments, a chemical modification is in the 5-position of the uracil. In some embodiments, a chemical modification is a N1-methyl pseudouridine. In some embodiments, 100% of the uracil in the open reading frame have a N1-methyl pseudouridine in the 5-position of the uracil.

In some embodiments, efficacy of RNA vaccines RNA (e.g., mRNA) can be significantly enhanced when combined with a flagellin adjuvant, in particular, when one or more antigen-encoding mRNAs is combined with an mRNA encoding flagellin.

RNA (e.g., mRNA) vaccines combined with the flagellin adjuvant (e.g., mRNA-encoded flagellin adjuvant) have superior properties in that they may produce much larger antibody titers and produce responses earlier than commercially available vaccine formulations. While not wishing to be bound by theory, it is believed that the RNA vaccines, for example, as mRNA polynucleotides, are better designed to produce the appropriate protein conformation upon translation, for both the antigen and the adjuvant, as the RNA (e.g., mRNA) vaccines co-opt natural cellular machinery. Unlike traditional vaccines, which are manufactured ex vivo and may trigger unwanted cellular responses, RNA (e.g., mRNA) vaccines are presented to the cellular system in a more native fashion.

Some embodiments of the present disclosure provide RNA (e.g., mRNA) vaccines that include at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one antigenic polypeptide or an immunogenic fragment thereof (e.g., an immunogenic fragment capable of inducing an immune response to the antigenic polypeptide) and at least one RNA (e.g., mRNA polynucleotide) having an open reading frame encoding a flagellin adjuvant.

In some embodiments, at least one flagellin polypeptide (e.g., encoded flagellin polypeptide) is a flagellin protein. In some embodiments, at least one flagellin polypeptide (e.g., encoded flagellin polypeptide) is an immunogenic flagellin fragment. In some embodiments, at least one flagellin polypeptide and at least one antigenic polypeptide are encoded by a single RNA (e.g., mRNA) polynucleotide. In other embodiments, at least one flagellin polypeptide and at least one antigenic polypeptide are each encoded by a different RNA polynucleotide.

Some embodiments of the present disclosure provide methods of inducing an antigen specific immune response in a subject, comprising administering to the subject a HIV vaccine in an amount effective to produce an antigen specific immune response.

In some aspects, vaccines of the invention (e.g., LNP-encapsulated mRNA vaccines) produce prophylactically- and/or therapeutically-efficacious levels, concentrations and/or titers of antigen-specific antibodies in the blood or serum of a vaccinated subject. As defined herein, the term antibody titer refers to the amount of antigen-specific antibody produces in s subject, e.g., a human subject. In exemplary embodiments, antibody titer is expressed as the inverse of the greatest dilution (in a serial dilution) that still gives a positive result. In exemplary embodiments, antibody titer is determined or measured by enzyme-linked immunosorbent assay (ELISA). In exemplary embodiments, antibody titer is determined or measured by neutralization assay, e.g., by microneutralization assay. In certain aspects, antibody titer measurement is expressed as a ratio, such as 1:40, 1:100, etc.

In exemplary embodiments of the invention, an efficacious vaccine produces an antibody titer of greater than 1:40, greater that 1:100, greater than 1:400, greater than 1:1000, greater than 1:2000, greater than 1:3000, greater than 1:4000, greater than 1:500, greater than 1:6000, greater than 1:7500, greater than 1:10000. In exemplary embodiments, the antibody titer is produced or reached by 10 days following vaccination, by 20 days following vaccination, by 30 days following vaccination, by 40 days following vaccination, or by 50 or more days following vaccination. In exemplary embodiments, the titer is produced or reached following a single dose of vaccine administered to the subject. In other embodiments, the titer is produced or reached following multiple doses, e.g., following a first and a second dose (e.g., a booster dose.)

In exemplary aspects of the invention, antigen-specific antibodies are measured in units of g/ml or are measured in units of IU/L (International Units per liter) or mIU/ml (milli International Units per ml). In exemplary embodiments of the invention, an efficacious vaccine produces >0.5 μg/ml, >0.1 μg/ml, >0.2 μg/ml, >0.35 μg/ml, >0.5 μg/ml, >1 μg/ml, >2 μg/ml, >5 μg/ml or >10 μg/ml. In exemplary embodiments of the invention, an efficacious vaccine produces >10 mIU/ml, >20 mIU/ml, >50 mIU/ml, >100 mIU/ml, >200 mIU/ml, >500 mIU/ml or >1000 mIU/ml. In exemplary embodiments, the antibody level or concentration is produced or reached by 10 days following vaccination, by 20 days following vaccination, by 30 days following vaccination, by 40 days following vaccination, or by 50 or more days following vaccination. In exemplary embodiments, the level or concentration is produced or reached following a single dose of vaccine administered to the subject. In other embodiments, the level or concentration is produced or reached following multiple doses, e.g., following a first and a second dose (e.g., a booster dose.) In exemplary embodiments, antibody level or concentration is determined or measured by enzyme-linked immunosorbent assay (ELISA). In exemplary embodiments, antibody level or concentration is determined or measured by neutralization assay, e.g., by microneutralization assay.

In some embodiments, the HIV vaccine includes at least one RNA polynucleotide having an open reading frame encoding at least one HIV antigenic polypeptide having at least one modification, at least one 5′ terminal cap, and is formulated within a lipid nanoparticle. 5′-capping of polynucleotides may be completed concomitantly during the in vitro-transcription reaction using the following chemical RNA cap analogs to generate the 5′-guanosine cap structure according to manufacturer protocols: 3′-O-Me-m7G(5′)ppp(5′) G [the ARCA cap]; G(5′)ppp(5′)A; G(5′)ppp(5′)G; m7G(5′)ppp(5′)A; m7G(5′)ppp(5′)G (New England BioLabs, Ipswich, Mass.). 5′-capping of modified RNA may be completed post-transcriptionally using a Vaccinia Virus Capping Enzyme to generate the “Cap 0” structure: m7G(5′)ppp(5′)G (New England BioLabs, Ipswich, Mass.). Cap 1 structure may be generated using both Vaccinia Virus Capping Enzyme and a 2′-O methyl-transferase to generate m7G(5′)ppp(5′)G-2′-O-methyl. Cap 2 structure may be generated from the Cap 1 structure followed by the 2′-O-methylation of the 5′-antepenultimate nucleotide using a 2′-0 methyl-transferase. Cap 3 structure may be generated from the Cap 2 structure followed by the 2′-O-methylation of the 5′-preantepenultimate nucleotide using a 2′-0 methyl-transferase. Enzymes are preferably derived from a recombinant source.

When transfected into mammalian cells, the modified mRNAs have a stability of from about 12 to about 18 hours or more than about 18 hours, e.g., 24, 36, 48, 60, 72, or greater than about 72 hours.

In some embodiments, a codon optimized RNA may, for instance, be one in which the levels of G/C are enhanced. The G/C-content of nucleic acid molecules may influence the stability of the RNA. RNA having an increased amount of guanine (G) and/or cytosine (C) residues may be functionally more stable than nucleic acids containing a large amount of adenine (A) and thymine (T) or uracil (U) nucleotides. WO02/098443 discloses a pharmaceutical composition containing an mRNA stabilized by sequence modifications in the translated region. Due to the degeneracy of the genetic code, the modifications work by substituting existing codons for those that promote greater RNA stability without changing the resulting amino acid. The approach is limited to coding regions of the RNA.

Modifications of polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides), including but not limited to chemical modification, that are useful in the compositions, vaccines, methods and synthetic processes of the present disclosure include, but are not limited to the following: 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine; 2-methylthio-N6-methyladenosine; 2-methylthio-N6-threonyl carbamoyladenosine; N6-glycinylcarbamoyladenosine; N6-isopentenyladenosine; N6-methyladenosine; N6-threonylcarbamoyladenosine; 1,2′-O-dimethyladenosine; 1-methyladenosine; 2′-O-methyladenosine; 2′-O-ribosyladenosine (phosphate); 2-methyladenosine; 2-methylthio-N6 isopentenyladenosine; 2-methylthio-N6-hydroxynorvalyl carbamoyladenosine; 2′-O-methyladenosine; 2′-O-ribosyladenosine (phosphate); Isopentenyladenosine; N6-(cis-hydroxyisopentenyl)adenosine; N6,2′-O-dimethyladenosine; N6,2′-O-dimethyladenosine; N6,N6,2′-O-trimethyladenosine; N6,N6-dimethyladenosine; N6-acetyladenosine; N6-hydroxynorvalylcarbamoyladenosine; N6-methyl-N6-threonylcarbamoyladenosine; 2-methyladenosine; 2-methylthio-N6-isopentenyladenosine; 7-deaza-adenosine; N1-methyl-adenosine; N6, N6 (dimethyl)adenine; N6-cis-hydroxy-isopentenyl-adenosine; a-thio-adenosine; 2 (amino)adenine; 2 (aminopropyl)adenine; 2 (methylthio) N6 (isopentenyl)adenine; 2-(alkyl)adenine; 2-(aminoalkyl)adenine; 2-(aminopropyl)adenine; 2-(halo)adenine; 2-(halo)adenine; 2-(propyl)adenine; 2′-Amino-2′-deoxy-ATP; 2′-Azido-2′-deoxy-ATP; 2′-Deoxy-2′-a-aminoadenosine TP; 2′-Deoxy-2′-a-azidoadenosine TP; 6 (alkyl)adenine; 6 (methyl)adenine; 6-(alkyl)adenine; 6-(methyl)adenine; 7 (deaza)adenine; 8 (alkenyl)adenine; 8 (alkynyl)adenine; 8 (amino)adenine; 8 (thioalkyl)adenine; 8-(alkenyl)adenine; 8-(alkyl)adenine; 8-(alkynyl)adenine; 8-(amino)adenine; 8-(halo)adenine; 8-(hydroxyl)adenine; 8-(thioalkyl)adenine; 8-(thiol)adenine; 8-azido-adenosine; aza adenine; deaza adenine; N6 (methyl)adenine; N6-(isopentyl)adenine; 7-deaza-8-aza-adenosine; 7-methyladenine; 1-Deazaadenosine TP; 2′Fluoro-N6-Bz-deoxyadenosine TP; 2′-OMe-2-Amino-ATP; 2′O-methyl-N6-Bz-deoxyadenosine TP; 2′-a-Ethynyladenosine TP; 2-aminoadenine; 2-Aminoadenosine TP; 2-Amino-ATP; 2′-a-Trifluoromethyladenosine TP; 2-Azidoadenosine TP; 2′-b-Ethynyladenosine TP; 2-Bromoadenosine TP; 2′-b-Trifluoromethyladenosine TP; 2-Chloroadenosine TP; 2′-Deoxy-2′,2′-difluoroadenosine TP; 2′-Deoxy-2′-a-mercaptoadenosine TP; 2′-Deoxy-2′-a-thiomethoxyadenosine TP; 2′-Deoxy-2′-b-aminoadenosine TP; 2′-Deoxy-2′-b-azidoadenosine TP; 2′-Deoxy-2′-b-bromoadenosine TP; 2′-Deoxy-2′-b-chloroadenosine TP; 2′-Deoxy-2′-b-fluoroadenosine TP; 2′-Deoxy-2′-b-iodoadenosine TP; 2′-Deoxy-2′-b-mercaptoadenosine TP; 2′-Deoxy-2′-b-thiomethoxyadenosine TP; 2-Fluoroadenosine TP; 2-lodoadenosine TP; 2-Mercaptoadenosine TP; 2-methoxy-adenine; 2-methylthio-adenine; 2-Trifluoromethyladenosine TP; 3-Deaza-3-bromoadenosine TP; 3-Deaza-3-chloroadenosine TP; 3-Deaza-3-fluoroadenosine TP; 3-Deaza-3-iodoadenosine TP; 3-Deazaadenosine TP; 4′-Azidoadenosine TP; 4′-Carbocyclic adenosine TP; 4′-Ethynyladenosine TP; 5′-Homo-adenosine TP; 8-Aza-ATP; 8-bromo-adenosine TP; 8-Trifluoromethyladenosine TP; 9-Deazaadenosine TP; 2-aminopurine; 7-deaza-2,6-diaminopurine; 7-deaza-8-aza-2,6-diaminopurine; 7-deaza-8-aza-2-aminopurine; 2,6-diaminopurine; 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine; 2-thiocytidine; 3-methylcytidine; 5-formylcytidine; 5-hydroxymethylcytidine; 5-methylcvtidine; N4-acetylcytidine; 2′-O-methylcytidine; 2′-O-methylcytidine; 5,2′-O-dimethylcytidine; 5-formyl-2′-O-methylcytidine; Lysidine; N4,2′-O-dimethylcytidine; N4-acetyl-2′-O-methylcytidine; N4-methylcytidine; N4,N4-Dimethyl-2′-OMe-Cytidine TP; 4-methylcytidine; 5-aza-cytidine; Pseudo-iso-cytidine; pyrrolo-cytidine; c-thio-cytidine; 2-(thio)cytosine; 2′-Amino-2′-deoxy-CTP; 2′-Azido-2′-deoxy-CTP; 2′-Deoxy-2′-a-aminocytidine TP; 2′-Deoxy-2′-a-azidocytidine TP; 3 (deaza) 5 (aza)cytosine; 3 (methyl)cytosine; 3-(alkyl)cytosine; 3-(deaza) 5 (aza)cytosine; 3-(methyl)cytidine; 4,2′-O-dimethylcytidine; 5 (halo)cytosine; 5 (methyl)cytosine; 5 (propynyl)cytosine; 5 (trifluoromethyl)cytosine; 5-(alkyl)cytosine; 5-(alkynyl)cytosine; 5-(halo)cytosine; 5-(propynyl)cytosine; 5-(trifluoromethyl)cytosine; 5-bromo-cytidine; 5-iodo-cytidine; 5-propynyl cytosine; 6-(azo)cytosine; 6-aza-cytidine; aza cytosine; deaza cytosine; N4 (acetyl)cytosine; 1-methyl-1-deaza-pseudoisocytidine; 1-methyl-pseudoisocytidine; 2-methoxy-5-methyl-cytidine; 2-methoxy-cytidine; 2-thio-5-methyl-cytidine; 4-methoxy-1-methyl-pseudoisocytidine; 4-methoxy-pseudoisocytidine; 4-thio-1-methyl-1-deaza-pseudoisocytidine; 4-thio-1-methyl-pseudoisocytidine; 4-thio-pseudoisocytidine; 5-aza-zebularine; 5-methyl-zebularine; pyrrolo-pseudoisocytidine; Zebularine; (E)-5-(2-Bromo-vinyl)cytidine TP; 2,2′-anhydro-cytidine TP hydrochloride; 2′Fluor-N4-Bz-cytidine TP; 2′Fluoro-N4-Acetyl-cytidine TP; 2′-O-Methyl-N4-Acetyl-cytidine TP; 2′O-methyl-N4-Bz-cytidine TP; 2′-a-Ethynylcytidine TP; 2′-a-Trifluoromethylcytidine TP; 2′-b-Ethynylcytidine TP; 2′-b-Trifluoromethylcytidine TP; 2′-Deoxy-2′,2′-difluorocytidine TP; 2′-Deoxy-2′-a-mercaptocytidine TP; 2′-Deoxy-2′-a-thiomethoxycytidine TP; 2′-Deoxy-2′-b-aminocytidine TP; 2′-Deoxy-2′-b-azidocytidine TP; 2′-Deoxy-2′-b-bromocytidine TP; 2′-Deoxy-2′-b-chlorocytidine TP; 2′-Deoxy-2′-b-fluorocytidine TP; 2′-Deoxy-2′-b-iodocytidine TP; 2′-Deoxy-2′-b-mercaptocytidine TP; 2′-Deoxy-2′-b-thiomethoxycytidine TP; 2′-O-Methyl-5-(1-propynyl)cytidine TP; 3′-Ethynylcytidine TP; 4′-Azidocytidine TP; 4′-Carbocyclic cytidine TP; 4′-Ethynylcytidine TP; 5-(1-Propynyl)ara-cytidine TP; 5-(2-Chloro-phenyl)-2-thiocytidine TP; 5-(4-Amino-phenyl)-2-thiocytidine TP; 5-Aminoallyl-CTP; 5-Cyanocytidine TP; 5-Ethynylara-cytidine TP; 5-Ethynylcytidine TP; 5′-Homo-cytidine TP; 5-Methoxycytidine TP; 5-Trifluoromethyl-Cytidine TP; N4-Amino-cytidine TP; N4-Benzoyl-cytidine TP; Pseudoisocytidine; 7-methylguanosine; N2,2′-O-dimethylguanosine; N2-methylguanosine; Wyosine; 1,2′-O-dimethylguanosine; 1-methylguanosine; 2′-O-methylguanosine; 2′-O-ribosylguanosine (phosphate); 2′-O-methylguanosine; 2′-O-ribosylguanosine (phosphate); 7-aminomethyl-7-deazaguanosine; 7-cyano-7-deazaguanosine; Archaeosine; Methyiwyosine; N2,7-dimethylguanosine; N2,N2,2′-O-trimethylguanosine; N2,N2,7-trimethylguanosine; N2,N2-dimethylguanosine; N2,7,2′-O-trimethylguanosine; 6-thio-guanosine; 7-deaza-guanosine; 8-oxo-guanosine; N1-methyl-guanosine; a-thio-guanosine; 2 (propyl)guanine; 2-(alkyl)guanine; 2′-Amino-2′-deoxy-GTP; 2′-Azido-2′-deoxy-GTP; 2′-Deoxy-2′-a-aminoguanosine TP; 2′-Deoxy-2′-a-azidoguanosine TP; 6 (methyl)guanine; 6-(alkyl)guanine; 6-(methyl)guanine; 6-methyl-guanosine; 7 (alkyl)guanine; 7 (deaza)guanine; 7 (methyl)guanine; 7-(alkyl)guanine; 7-(deaza)guanine; 7-(methyl)guanine; 8 (alkyl)guanine; 8 (alkynyl)guanine; 8 (halo)guanine; 8 (thioalkyl)guanine; 8-(alkenyl)guanine; 8-(alkyl)guanine; 8-(alkynyl)guanine; 8-(amino)guanine; 8-(halo)guanine; 8-(hydroxyl)guanine; 8-(thioalkyl)guanine; 8-(thiol)guanine; aza guanine; deaza guanine; N (methyl)guanine; N-(methyl)guanine; 1-methyl-6-thio-guanosine; 6-methoxy-guanosine; 6-thio-7-deaza-8-aza-guanosine; 6-thio-7-deaza-guanosine; 6-thio-7-methyl-guanosine; 7-deaza-8-aza-guanosine; 7-methyl-8-oxo-guanosine; N2,N2-dimethyl-6-thio-guanosine; N2-methyl-6-thio-guanosine; 1-Me-GTP; 2′Fluoro-N2-isobutyl-guanosine TP; 2′O-methyl-N2-isobutyl-guanosine TP; 2′-a-Ethynylguanosine TP; 2′-a-Trifluoromethylguanosine TP; 2′-b-Ethynylguanosine TP; 2′-b-Trifluoromethylguanosine TP; 2′-Deoxy-2′,2′-difluoroguanosine TP; 2′-Deoxy-2′-a-mercaptoguanosine TP; 2′-Deoxy-2′-a-thiomethoxyguanosine TP; 2′-Deoxy-2-b-aminoguanosine TP; 2′-Deoxy-2′-b-azidoguanosine TP; 2′-Deoxy-2′-b-bromoguanosine TP; 2′-Deoxy-2′-b-chloroguanosine TP; 2′-Deoxy-2′-b-fluoroguanosine TP; 2′-Deoxy-2′-b-iodoguanosine TP; 2′-Deoxy-2′-b-mercaptoguanosine TP; 2′-Deoxy-2′-b-thiomethoxyguanosine TP; 4′-Azidoguanosine TP; 4′-Carbocyclic guanosine TP; 4′-Ethynylguanosine TP; 5′-Homo-guanosine TP; 8-bromo-guanosine TP; 9-Deazaguanosine TP; N2-isobutyl-guanosine TP; 1-methylinosine; Inosine; 1,2′-O-dimethylinosine; 2′-O-methylinosine; 7-methylinosine; 2′-O-methylinosine; Epoxyqueuosine; galactosyl-queuosine; Mannosylqueuosine; Queuosine; allyamino-thymidine; aza thymidine; deaza thymidine; deoxy-thymidine; 2′-O-methyluridine; 2-thiouridine; 3-methyluridine; 5-carboxymethyluridine; 5-hydroxyuridine; 5-methyluridine; 5-taurinomethyl-2-thiouridine; 5-taurinomethyluridine; Dihydrouridine; Pseudouridine; (3-(3-amino-3-carboxypropyl)uridine; 1-methyl-3-(3-amino-5-carboxypropyl)pseudouridine; 1-methylpseduouridine; 1-ethyl-pseudouridine; 2′-O-methyluridine; 2′-O-methylpseudouridine; 2′-O-methyluridine; 2-thio-2′-O-methyluridine; 3-(3-amino-3-carboxypropyl)uridine; 3,2′-O-dimethyluridine; 3-Methyl-pseudo-Uridine TP; 4-thiouridine; 5-(carboxyhydroxymethyl)uridine; 5-(carboxyhydroxymethyl)uridine methyl ester; 5,2′-O-dimethyluridine; 5,6-dihydro-uridine; 5-aminomethyl-2-thiouridine; 5-carbamoylmethyl-2′-O-methyluridine; 5-carbamoylmethyluridine; 5-carboxyhydroxymethyluridine; 5-carboxyhydroxymethyluridine methyl ester; 5-carboxymethylaminomethyl-2′-O-methyluridine; 5-carboxymethylaminomethyl-2-thiouridine; 5-carboxymethylaminomethyl-2-thiouridine; 5-carboxymethylaminomethyluridine; 5-carboxymethylaminomethyluridine; 5-Carbamoylmethyluridine TP; 5-methoxycarbonylmethyl-2′-O-methyluridine; 5-methoxycarbonylmethyl-2-thiouridine; 5-methoxycarbonylmethyluridine; 5-methyluridine,), 5-methoxyuridine; 5-methyl-2-thiouridine; 5-methylaminomethyl-2-selenouridine; 5-methylaminomethyl-2-thiouridine; 5-methylaminomethyluridine; 5-Methyldihydrouridine; 5-Oxyacetic acid-Uridine TP; 5-Oxyacetic acid-methyl ester-Uridine TP; N1-methyl-pseudo-uracil; NT-ethyl-pseudo-uracil; uridine 5-oxyacetic acid; uridine 5-oxyacetic acid methyl ester; 3-(3-Amino-3-carboxypropyl)-Uridine TP; 5-(iso-Pentenylaminomethyl)-2-thiouridine TP; 5-(iso-Pentenylaminomethyl)-2′-O-methyluridine TP; 5-(iso-Pentenylaminomethyl)uridine TP; 5-propynyl uracil; a-thio-uridine; 1 (aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouracil; 1 (aminoalkylaminocarbonylethylenyl)-pseudouracil; 1 (aminocarbonylethylenyl)-2(thio)-pseudouracil; 1 (aminocarbonylethylenyl)-2,4-(dithio)pseudouracil; 1 (aminocarbonylethylenyl)-4 (thio)pseudouracil; 1 (aminocarbonylethylenyl)-pseudouracil; 1 substituted 2(thio)-pseudouracil; 1 substituted 2,4-(dithio)pseudouracil; 1 substituted 4 (thio)pseudouracil; 1 substituted pseudouracil; 1-(aminoalkylamino-carbonylethylenyl)-2-(thio)-pseudouracil; 1-Methyl-3-(3-amino-3-carboxypropyl) pseudouridine TP; 1-Methyl-3-(3-amino-3-carboxypropyl)pseudo-UTP; 1-Methyl-pseudo-UTP; 1-Ethyl-pseudo-UTP; 2 (thio)pseudouracil; 2′ deoxy uridine; 2′ fluorouridine; 2-(thio)uracil; 2,4-(dithio)psuedouracil; 2′ methyl, 2′amino, 2′azido, 2′fluoro-guanosine; 2′-Amino-2′-deoxy-UTP; 2′-Azido-2′-deoxy-UTP; 2′-Azido-deoxyuridine TP; 2′-O-methylpseudouridine; 2′ deoxy uridine; 2′ fluorouridine; 2′-Deoxy-2′-a-aminouridine TP; 2-Deoxy-2′-a-azidouridine TP; 2-methylpseudouridine; 3 (3 amino-3 carboxypropyl)uracil; 4 (thio)pseudouracil; 4-(thio)pseudouracil; 4-(thio)uracil; 4-thiouracil; 5 (1,3-diazole-1-alkyl)uracil; 5 (2-aminopropyl)uracil; 5 (aminoalkyl)uracil; 5 (dimethylaminoalkyl)uracil; 5 (guanidiniumalkyl)uracil; 5 (methoxycarbonylmethyl)-2-(thio)uracil; 5 (methoxycarbonyl-methyl)uracil; 5 (methyl) 2 (thio)uracil; 5 (methyl) 2,4 (dithio)uracil; 5 (methyl) 4 (thio)uracil; 5 (methylaminomethyl)-2 (thio)uracil; 5 (methylaminomethyl)-2,4 (dithio)uracil; 5 (methylaminomethyl)-4 (thio)uracil; 5 (propynyl)uracil; 5 (trifluoromethyl)uracil; 5-(2-aminopropyl)uracil; 5-(alkyl)-2-(thio)pseudouracil; 5-(alkyl)-2,4 (dithio)pseudouracil; 5-(alkyl)-4 (thio)pseudouracil; 5-(alkyl)pseudouracil; 5-(alkyl)uracil; 5-(alkynyl)uracil; 5-(allylamino)uracil; 5-(cyanoalkyl)uracil; 5-(dialkylaminoalkyl)uracil; 5-(dimethylaminoalkyl)uracil; 5-(guanidiniumalkyl)uracil; 5-(halo)uracil; 5-(1,3-diazole-1-alkyl)uracil; 5-(methoxy)uracil; 5-(methoxycarbonylmethyl)-2-(thio)uracil; 5-(methoxycarbonyl-methyl)uracil; 5-(methyl) 2(thio)uracil; 5-(methyl) 2,4 (dithio)uracil; 5-(methyl) 4 (thio)uracil; 5-(methyl)-2-(thio)pseudouracil; 5-(methyl)-2,4 (dithio)pseudouracil; 5-(methyl)-4 (thio)pseudouracil; 5-(methyl)pseudouracil; 5-(methylaminomethyl)-2 (thio)uracil; 5-(methylaminomethyl)-2,4(dithio)uracil; 5-(methylaminomethyl)-4-(thio)uracil; 5-(propynyl)uracil; 5-(trifluoromethyl)uracil; 5-aminoallyl-uridine; 5-bromo-uridine; 5-iodo-uridine; 5-uracil; 6 (azo)uracil; 6-(azo)uracil; 6-aza-uridine; allyamino-uracil; aza uracil; deaza uracil; N3 (methyl)uracil; Pseudo-UTP-1-2-ethanoic acid; Pseudouracil; 4-Thio-pseudo-UTP; 1-carboxymethyl-pseudouridine; 1-methyl-1-deaza-pseudouridine; 1-propynyl-uridine; 1-taurinomethyl-1-methyl-uridine; 1-taurinomethyl-4-thio-uridine; 1-taurinomethyl-pseudouridine; 2-methoxy-4-thio-pseudouridine; 2-thio-1-methyl-1-deaza-pseudouridine; 2-thio-1-methyl-pseudouridine; 2-thio-5-aza-uridine; 2-thio-dihydropseudouridine; 2-thio-dihydrouridine; 2-thio-pseudouridine; 4-methoxy-2-thio-pseudouridine; 4-methoxy-pseudouridine; 4-thio-1-methyl-pseudouridine; 4-thio-pseudouridine; 5-aza-uridine; Dihydropseudouridine; (+) 1-(2-Hydroxypropyl)pseudouridine TP; (2R)-1-(2-Hydroxypropyl)pseudouridine TP; (2S)-1-(2-Hydroxypropyl)pseudouridine TP; (E)-5-(2-Bromo-vinyl)ara-uridine TP; (E)-5-(2-Bromo-vinyl)uridine TP; (Z)-5-(2-Bromo-vinyl)ara-uridine TP; (Z)-5-(2-Bromo-vinyl)uridine TP; 1-(2,2,2-Trifluoroethyl)-pseudo-UTP; 1-(2,2,3,3,3-Pentafluoropropyl)pseudouridine TP; 1-(2,2-Diethoxyethyl)pseudouridine TP; 1-(2,4,6-Trimethylbenzyl)pseudouridine TP; 1-(2,4,6-Trimethyl-benzyl)pseudo-UTP; 1-(2,4,6-Trimethyl-phenyl)pseudo-UTP; 1-(2-Amino-2-carboxyethyl)pseudo-UTP; 1-(2-Amino-ethyl)pseudo-UTP; 1-(2-Hydroxyethyl)pseudouridine TP; 1-(2-Methoxyethyl)pseudouridine TP; 1-(3,4-Bis-trifluoromethoxybenzyl)pseudouridine TP; 1-(3,4-Dimethoxybenzyl)pseudouridine TP; 1-(3-Amino-3-carboxypropyl)pseudo-UTP; 1-(3-Amino-propyl)pseudo-UTP; 1-(3-Cyclopropyl-prop-2-ynyl)pseudouridine TP; 1-(4-Amino-4-carboxybutyl)pseudo-UTP; 1-(4-Amino-benzyl)pseudo-UTP; 1-(4-Amino-butyl)pseudo-UTP; 1-(4-Amino-phenyl)pseudo-UTP; 1-(4-Azidobenzyl)pseudouridine TP; 1-(4-Bromobenzyl)pseudouridine TP; 1-(4-Chlorobenzyl)pseudouridine TP; 1-(4-Fluorobenzyl)pseudouridine TP; 1-(4-Iodobenzyl)pseudouridine TP; 1-(4-Methanesulfonylbenzyl)pseudouridine TP; 1-(4-Methoxybenzyl)pseudouridine TP; 1-(4-Methoxy-benzyl)pseudo-UTP; 1-(4-Methoxy-phenyl)pseudo-UTP; 1-(4-Methylbenzyl)pseudouridine TP; 1-(4-Methyl-benzyl)pseudo-UTP; 1-(4-Nitrobenzyl)pseudouridine TP; 1-(4-Nitro-benzyl)pseudo-UTP; 1(4-Nitro-phenyl)pseudo-UTP; 1-(4-Thiomethoxybenzyl)pseudouridine TP; 1-(4-Trifluoromethoxybenzyl)pseudouridine TP; 1-(4-Trifluoromethylbenzyl)pseudouridine TP; 1-(5-Amino-pentyl)pseudo-UTP; 1-(6-Amino-hexyl)pseudo-UTP; 1,6-Dimethyl-pseudo-UTP; 1-[3-(2-{2-[2-(2-Aminoethoxy)-ethoxy]-ethoxy}-ethoxy)-propionyl]pseudouridine TP; 1-{3-[2-(2-Aminoethoxy)-ethoxy]-propionyl} pseudouridine TP; 1-Acetylpseudouridine TP; 1-Alkyl-6-(1-propynyl)-pseudo-UTP; 1-Alkyl-6-(2-propynyl)-pseudo-UTP; 1-Alkyl-6-allyl-pseudo-UTP; 1-Alkyl-6-ethynyl-pseudo-UTP; 1-Alkyl-6-homoallyl-pseudo-UTP; 1-Alkyl-6-vinyl-pseudo-UTP; 1-Allylpseudouridine TP; 1-Aminomethyl-pseudo-UTP; 1-Benzoylpseudouridine TP; 1-Benzyloxymethylpseudouridine TP; 1-Benzyl-pseudo-UTP; 1-Biotinyl-PEG2-pseudouridine TP; 1-Biotinylpseudouridine TP; 1-Butyl-pseudo-UTP; 1-Cyanomethylpseudouridine TP; 1-Cyclobutylmethyl-pseudo-UTP; 1-Cyclobutyl-pseudo-UTP; 1-Cvcloheptylmethyl-pseudo-UTP; 1-Cycloheptyl-pseudo-UTP; 1-Cyclohexylmethyl-pseudo-UTP; 1-Cyclohexyl-pseudo-UTP; 1-Cyclooctylmethyl-pseudo-UTP; 1-Cyclooctyl-pseudo-UTP; 1-Cyclopentylmethyl-pseudo-UTP; 1-Cyclopentyl-pseudo-UTP; 1-Cyclopropylmethyl-pseudo-UTP; 1-Cyclopropyl-pseudo-UTP; 1-Ethyl-pseudo-UTP; 1-Hexyl-pseudo-UTP; 1-Homoallylpseudouridine TP; 1-Hydroxymethylpseudouridine TP; 1-iso-propyl-pseudo-UTP; 1-Me-2-thio-pseudo-UTP; 1-Me-4-thio-pseudo-UTP; 1-Me-alpha-thio-pseudo-UTP; 1-Methanesulfonylmethylpseudouridine TP; 1-Methoxymethylpseudouridine TP; 1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-UTP; 1-Methyl-6-(4-morpholino)-pseudo-UTP; 1-Methyl-6-(4-thiomorpholino)-pseudo-UTP; 1-Methyl-6-(substituted phenyl)pseudo-UTP; 1-Methyl-6-amino-pseudo-UTP; 1-Methyl-6-azido-pseudo-UTP; 1-Methyl-6-bromo-pseudo-UTP; 1-Methyl-6-butyl-pseudo-UTP; 1-Methyl-6-chloro-pseudo-UTP; 1-Methyl-6-cyano-pseudo-UTP; 1-Methyl-6-dimethylamino-pseudo-UTP; 1-Methyl-6-ethoxy-pseudo-UTP; 1-Methyl-6-ethylcarboxylate-pseudo-UTP; 1-Methyl-6-ethyl-pseudo-UTP; 1-Methyl-6-fluoro-pseudo-UTP; 1-Methyl-6-formyl-pseudo-UTP; 1-Methyl-6-hydroxyamino-pseudo-UTP; 1-Methyl-6-hydroxy-pseudo-UTP; 1-Methyl-6-iodo-pseudo-UTP; 1-Methyl-6-iso-propyl-pseudo-UTP; 1-Methyl-6-methoxy-pseudo-UTP; 1-Methyl-6-methylamino-pseudo-UTP; 1-Methyl-6-phenyl-pseudo-UTP; 1-Methyl-6-propyl-pseudo-UTP; 1-Methyl-6-tert-butyl-pseudo-UTP; 1-Methyl-6-trifluoromethoxy-pseudo-UTP; 1-Methyl-6-trifluoromethyl-pseudo-UTP; 1-Morpholinomethylpseudouridine TP; 1-Pentyl-pseudo-UTP; 1-Phenyl-pseudo-UTP; 1-Pivaloylpseudouridine TP; 1-Propargylpseudouridine TP; 1-Propyl-pseudo-UTP; 1-propynyl-pseudouridine; 1-p-tolyl-pseudo-UTP; 1-tert-Butyl-pseudo-UTP; 1-Thiomethoxymethylpseudouridine TP; 1-Thiomorpholinomethylpseudouridine TP; 1-Trifluoroacetylpseudouridine TP; 1-Trifluoromethyl-pseudo-UTP; 1-Vinylpseudouridine TP; 2,2′-anhydro-uridine TP; 2′-bromo-deoxyuridine TP; 2′-F-5-Methyl-2′-deoxy-UTP; 2′-OMe-5-Me-UTP; 2′-OMe-pseudo-UTP; 2′-a-Ethynyluridine TP; 2′-a-Trifluoromethyluridine TP; 2′-b-Ethynyluridine TP; 2′-b-Trifluoromethyluridine TP; 2′-Deoxy-2′,2′-difluorouridine TP; 2′-Deoxy-2′-a-mercaptouridine TP; 2′-Deoxy-2′-a-thiomethoxyuridine TP; 2′-Deoxy-2′-b-aminouridine TP; 2′-Deoxy-2′-b-azidouridine TP; 2′-Deoxy-2′-b-bromouridine TP; 2′-Deoxy-2′-b-chlorouridine TP; 2′-Deoxy-2′-b-fluorouridine TP; 2′-Deoxy-2′-b-iodouridine TP; 2′-Deoxy-2′-b-mercaptouridine TP; 2′-Deoxy-2′-b-thiomethoxyuridine TP; 2-methoxy-4-thio-uridine; 2-methoxyuridine; 2′-O-Methyl-5-(1-propynyl)uridine TP; 3-Alkyl-pseudo-UTP; 4′-Azidouridine TP; 4′-Carbocyclic uridine TP; 4′-Ethynyluridine TP; 5-(1-Propynyl)ara-uridine TP; 5-(2-Furanyl)uridine TP; 5-Cyanouridine TP; 5-Dimethylaminouridine TP; 5′-Homo-uridine TP; 5-iodo-2′-fluoro-deoxyuridine TP; 5-Phenylethynyluridine TP; 5-Trideuteromethyl-6-deuterouridine TP; 5-Trifluoromethyl-Uridine TP; 5-Vinylarauridine TP; 6-(2,2,2-Trifluoroethyl)-pseudo-UTP; 6-(4-Morpholino)-pseudo-UTP; 6-(4-Thiomorpholino)-pseudo-UTP; 6-(Substituted-Phenyl)-pseudo-UTP; 6-Amino-pseudo-UTP; 6-Azido-pseudo-UTP; 6-Bromo-pseudo-UTP; 6-Butyl-pseudo-UTP; 6-Chloro-pseudo-UTP; 6-Cyano-pseudo-UTP; 6-Dimethylamino-pseudo-UTP; 6-Ethoxy-pseudo-UTP; 6-Ethylcarboxylate-pseudo-UTP; 6-Ethyl-pseudo-UTP; 6-Fluoro-pseudo-UTP; 6-Formyl-pseudo-UTP; 6-Hydroxyamino-pseudo-UTP; 6-Hydroxy-pseudo-UTP; 6-Iodo-pseudo-UTP; 6-iso-Propyl-pseudo-UTP; 6-Methoxy-pseudo-UTP; 6-Methylamino-pseudo-UTP; 6-Methyl-pseudo-UTP; 6-Phenyl-pseudo-UTP; 6-Phenyl-pseudo-UTP; 6-Propyl-pseudo-UTP; 6-tert-Butyl-pseudo-UTP; 6-Trifluoromethoxy-pseudo-UTP; 6-Trifluoromethyl-pseudo-UTP; Alpha-thio-pseudo-UTP; Pseudouridine 1-(4-methylbenzenesulfonic acid) TP; Pseudouridine 1-(4-methylbenzoic acid) TP; Pseudouridine TP 1-[3-(2-ethoxy)]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-(2-ethoxy)-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-{2(2-ethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-ethoxy)-ethoxy}] propionic acid; Pseudouridine TP 1-methylphosphonic acid; Pseudouridine TP 1-methylphosphonic acid diethyl ester; Pseudo-UTP-N1-3-propionic acid; Pseudo-UTP-N1-4-butanoic acid; Pseudo-UTP-N1-5-pentanoic acid; Pseudo-UTP-N1-6-hexanoic acid; Pseudo-UTP-N1-7-heptanoic acid; Pseudo-UTP-N1-methyl-p-benzoic acid; Pseudo-UTP-N1-p-benzoic acid; Wybutosine; Hydroxywybutosine; Isowyosine; Peroxywybutosine; undermodified hydroxywybutosine; 4-demethylwyosine; 2,6-(diamino)purine; 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl: 1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 1,3,5-(triaza)-2,6-(dioxa)-naphthalene; 2 (amino)purine; 2,4,5-(trimethyl)phenyl; 2′ methyl, 2′amino, 2′azido, 2′fluoro-cytidine; 2′ methyl, 2′amino, 2′azido, 2′fluoro-adenine; 2′methyl, 2′amino, 2′azido, 2′fluoro-uridine; 2′-amino-2′-deoxyribose; 2-amino-6-Chloro-purine; 2-aza-inosinyl; 2′-azido-2′-deoxyribose; 2′fluoro-2′-deoxyribose; 2′-fluoro-modified bases; 2′-O-methyl-ribose; 2-oxo-7-aminopyridopyrimidin-3-yl; 2-oxo-pyridopyrimidine-3-yl; 2-pyridinone; 3 nitropyrrole; 3-(methyl)-7-(propynyl)isocarbostyrilyl; 3-(methyl)isocarbostvrilyl; 4-(fluoro)-6-(methyl)benzimidazole; 4-(methyl)benzimidazole; 4-(methyl)indolyl; 4,6-(dimethyl)indolyl; 5 nitroindole; 5 substituted pyrimidines; 5-(methyl)isocarbostyrilyl; 5-nitroindole; 6-(aza)pyrimidine; 6-(azo)thymine; 6-(methyl)-7-(aza)indolyl; 6-chloro-purine; 6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; 7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aza)indolyl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazinl-yl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(guanidiniumalkyl-hydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(propynyl)isocarbostyrilyl; 7-(propynyl)isocarbostyrilyl, propynyl-7-(aza)indolyl; 7-deaza-inosinyl; 7-substituted 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-substituted 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 9-(methyl)-imidizopyridinyl; Aminoindolyl; Anthracenyl; bis-ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; bis-ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Difluorotolyl; Hypoxanthine; Imidizopyridinyl; Inosinyl; Isocarbostyrilyl; Isoguanisine; N2-substituted purines; N6-methyl-2-amino-purine; N6-substituted purines; N-alkylated derivative; Napthalenyl; Nitrobenzimidazolyl; Nitroimidazolyl; Nitroindazolyl; Nitropyrazolyl; Nubularine; 06-substituted purines; O-alkylated derivative; ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; ortho-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Oxoformycin TP; para-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; para-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Pentacenyl; Phenanthracenyl; Phenyl; propynyl-7-(aza)indolyl; Pyrenyl; pyridopyrimidin-3-yl; pyridopyrimidin-3-yl, 2-oxo-7-aminopyridopyrimidin-3-yl; pyrrolo-pyrimidin-2-on-3-yl; Pyrrolopyrimidinyl; Pyrrolopyrizinyl; Stilbenzyl; substituted 1,2,4-triazoles; Tetracenyl; Tubercidine; Xanthine; Xanthosine-5′-TP; 2-thio-zebularine; 5-aza-2-thio-zebularine; 7-deaza-2-amino-purine; pyridin-4-one ribonucleoside; 2-Amino-riboside-TP; Formycin A TP; Formycin B TP; Pyrrolosine TP; 2′-OH-ara-adenosine TP; 2′-OH-ara-cytidine TP; 2′-OH-ara-uridine TP; 2′-OH-ara-guanosine TP; 5-(2-carbomethoxyvinyl)uridine TP; and N6-(19-Amino-pentaoxanonadecyl)adenosine TP.

In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) include a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases.

In some embodiments, modified nucleobases in polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) are selected from the group consisting of pseudouridine (p), 2-thiouridine (s2U), 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methyluridine, 5-methoxyuridine, 2′-O-methyl uridine, 1-methyl-pseudouridine (mly), 1-ethyl-pseudouridine (elyi), 5-methoxy-uridine (mo5U), 5-methyl-cytidine (m5C), a-thio-guanosine, a-thio-adenosine, 5-cyano uridine, 4′-thio uridine 7-deaza-adenine, 1-methyl-adenosine (mlA), 2-methyl-adenine (m2A), N6-methyl-adenosine (m6A), and 2,6-Diaminopurine, (I), 1-methyl-inosine (mlI), wyosine (imG), methylwyosine (mimG), 7-deaza-guanosine, 7-cyano-7-deaza-guanosine (preQ0), 7-aminomethyl-7-deaza-guanosine (preQ1), 7-methyl-guanosine (m7G), 1-methyl-guanosine (mlG), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 2,8-dimethyladenosine, 2-geranylthiouridine, 2-lysidine, 2-selenouridine, 3-(3-amino-3-carboxypropyl)-5,6-dihydrouridine, 3-(3-amino-3-carboxypropyl)pseudouridine, 3-methylpseudouridine, 5-(carboxyhydroxymethyl)-2′-O-methyluridine methyl ester, 5-aminomethyl-2-geranylthiouridine, 5-aminomethyl-2-selenouridine, 5-aminomethyluridine, 5-carbamoylhydroxymethyluridine, 5-carbamoylmethyl-2-thiouridine, 5-carboxymethyl-2-thiouridine, 5-carboxymethylaminomethyl-2-geranylthiouridine, 5-carboxymethylaminomethyl-2-selenouridine, 5-cyanomethyluridine, 5-hydroxycytidine, 5-methylaminomethyl-2-geranylthiouridine, 7-aminocarboxypropyl-demethylwyosine, 7-aminocarboxypropylwyosine, 7-aminocarboxypropylwyosine methyl ester, 8-methyladenosine, N4,N4-dimethylcytidine, N6-formyladenosine, N6-hydroxymethyladenosine, agmatidine, cyclic N6-threonylcarbamoyladenosine, glutamyl-queuosine, methylated undermodified hydroxywybutosine, N4,N4,2′-O-trimethylcytidine, geranylated 5-methylaminomethyl-2-thiouridine, geranylated 5-carboxymethylaminomethyl-2-thiouridine, Qbase, preQObase, preQIbase, and combinations of two or more thereof. In some embodiments, the at least one chemically modified nucleoside is selected from the group consisting of pseudouridine, 1-methyl-pseudouridine, 1-ethyl-pseudouridine, 5-methylcytosine, 5-methoxyuridine, and a combination thereof. In some embodiments, the polyribonucleotide (e.g., RNA polyribonucleotide, such as mRNA polyribonucleotide) includes a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases. In some embodiments, polynucleotides (e.g., RNA polynucleotides, such as mRNA polynucleotides) include a combination of at least two (e.g., 2, 3, 4 or more) of the aforementioned modified nucleobases.

The expressible nucleic acid sequence of the present disclosure may be partially or fully modified along the entire length of the molecule. For example, one or more or all or a given type of nucleotide (e.g., purine or pyrimidine, or any one or more or all of A, G, U, C) may be uniformly modified in a polynucleotide of the invention, or in a given predetermined sequence region thereof (e.g., in the mRNA including or excluding the polyA tail). In some embodiments, all nucleotides X in a polynucleotide of the present disclosure (or in a given sequence region thereof) are modified nucleotides, wherein X may be any one of nucleotides A, G, U, C, or any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U, A+G+C, G+U+C, or A+G+C.

The polynucleotide may contain from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e., any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%, from 1% to 252%, from 1T % to 50%, from about 1T % to about 60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 10% to 95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 95%, from 90% to 100%, and from 95% to 100%). It will be understood that any remaining percentage is accounted for by the presence of unmodified A, G, U, or C.

The nucleic acid sequences may contain at a minimum 1% and at maximum 100% modified nucleotides, or any intervening percentage, such as at least 5% modified nucleotides, at least 10% modified nucleotides, at least 25% modified nucleotides, at least 50% modified nucleotides, at least 80% modified nucleotides, or at least 90% modified nucleotides. For example, the polynucleotides may contain a modified pyrimidine such as a modified uracil or cytosine. In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the uracil in the polynucleotide is replaced with a modified uracil (e.g., a 5-substituted uracil). The modified uracil can be replaced by a compound having a single unique structure, or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4, or more unique structures). In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90%, or 100% of the cytosine in the polynucleotide is replaced with a modified cytosine (e.g., a 5-substituted cytosine). The modified cytosine can be replaced by a compound having a single unique structure, or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4, or more unique structures).

Thus, in some embodiments, the RNA vaccines and/or RNA nucleic acid sequences comprise a 5′UTR element, an optionally codon optimized open reading frame, and a 3′UTR element, a poly(A) sequence and/or a polyadenylation signal wherein the RNA is not chemically modified.

Viral vaccines of the present disclosure comprise at least one RNA polynucleotide, such as a mRNA (e.g., modified mRNA). mRNA, for example, is transcribed in vitro from template DNA, referred to as an “in vitro transcription template.” In some embodiments, the at least one RNA polynucleotide has at least one chemical modification. The at least one chemical modification may include, but is expressly not limited to, any modification described herein.

In vitro transcription of RNA is known in the art and is described in WO/2014/152027, which is incorporated by reference herein in its entirety. For example, in some embodiments, the RNA transcript is generated using a non-amplified, linearized DNA template in an in vitro transcription reaction to generate the RNA transcript. In some embodiments, the RNA transcript is capped via enzymatic capping. In some embodiments, the RNA transcript is purified via chromatographic methods, e.g., use of an oligo dT substrate. Some embodiments exclude the use of DNase. In some embodiments, the RNA transcript is synthesized from a non-amplified, linear DNA template coding for the gene of interest via an enzymatic in vitro transcription reaction utilizing a T7 phage RNA polymerase and nucleotide triphosphates of the desired chemistry. Any number of RNA polymerases or variants may be used in the method of the present invention. The polymerase may be selected from, but is not limited to, a phage RNA polymerase, e.g., a T7 RNA polymerase, a T3 RNA polymerase, a SP6 RNa polymerase, and/or mutant polymerases such as, but not limited to, polymerases able to incorporate modified nucleic acids and/or modified nucleotides, including chemically modified nucleic acids and/or nucleotides.

In some embodiments, a non-amplified, linearized plasmid DNA is utilized as the template DNA for in vitro transcription. In some embodiments, the template DNA is isolated DNA. In some embodiments, the template DNA is cDNA. In some embodiments, the cDNA is formed by reverse transcription of a RNA polynucleotide, for example, but not limited to HIV RNA, e.g. HIV mRNA. In some embodiments, cells, e.g., bacterial cells, e.g., E. coli, e.g., DH-1 cells are transfected with the plasmid DNA template. In some embodiments, the transfected cells are cultured to replicate the plasmid DNA which is then isolated and purified. In some embodiments, the DNA template includes a RNA polymerase promoter, e.g., a T7 promoter located 5′ to and operably linked to the gene of interest.

E. Vaccines

Disclosed are vaccines comprising a first amino acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any linker sequence provided herein; and/or a second amino acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one or combination of viral antigens (such as any one or combination of gp41 or gp120 nucleic acid sequences) disclosed herein. In some embodiments, the vaccines are free of a nucleic acid sequence that encodes an HIV transmembrane domain (gp41). In some cases the vaccine is a DNA or RNA vaccine that, upon administration to a subject and upon contact with a cell, encodes for a soluble retorviral trimer molecule. In some cases the vaccine is a DNA or RNA vaccine that, upon administration to a subject and upon contact with a cell, encodes for a soluble HIV ENV trimer molecule.

In some embodiments, the vaccines further comprise a linker fusing a first and a second nucleic acid sequence that encodes an amino acid sequence that is a fusion protein. For example, the linker can be an amino acid sequence comprising at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to SEQ ID NO:8.

F. Kits

The materials described above as well as other materials can be packaged together in any suitable combination as a kit useful for performing, or aiding in the performance of, the disclosed method. It is useful if the kit components in a given kit are designed and adapted for use together in the disclosed method. For example disclosed are kits comprising any of the elements of the disclosed nucleic acid compositions. For example, disclosed are kits comprising nucleic acid sequences comprising a leader sequence, a linker sequence, a nucleic acid sequence encoding a soluble retorviral envelope polypeptide. In some embodiments, the kits can further comprise a plasmid backbone.

EXAMPLES 1. Methods

i. DNA Design and Plasmid Synthesis

Amino acid sequences for BG505_MD39 based stabilized trimers were obtained from Kulp et al[8]. These sequences were then RNA and codon optimized as well as optimizing for GC content and secondary structure. Additionally, an optimized IgE leader sequence was added to the C term of the protein to provide efficient processing and secretion. All plasmid inserts were cloned into our modified pVAX1 backbone. Additional mutations were made to the BG505_MD39 base trimer to explore cleavage dependence, circular permutations, adding glycosylation to the bottom of the trimer, creating strings of trimers as well as linking the trimers to the membrane by including a transmembrane (PDGFR) domain.

Plasmids that encode the HIV Envelope BG505 WT was obtained from GenBank and produced. Point mutations were made for BG505 T332N, BG505 T332N S241N, BG505 T332N T456N. MG505, HIV backbone delta Env and MLV plasmids were obtained from NIH AIDS reagents resources. Plasmids for 11A and 12N antibodies were synthesized by Genscript and cloned into the modified pVAX1 backbone.

ii. Cell Lines, Transfection and Recombinant Antibody Purification.

HEK 293T cells and TZM-bl cells were maintained in DMEM supplemented with 10% of heat inactivated fetal bovine serum. Expi293F cells were maintained in Expi293 expression medium.

To produce recombinant HIV monoclonal antibodies for assay and controls, Expi293F cells were transfected following manufactures protocol for Expifectamin. Transfection enhancers were added 18 hours after transfection and supernatants were harvested 6 days after transfection. Protein G agarose was then used following manufactures protocol to purify out the IgG. Purity was confirmed with commassie staining of SDS-page gels and quantified using the quantification ELISA described below.

Pseudotype viruses were produced by transfecting HEK 293T cells with plasmid expressing the Env of interest with the plasmid expressing the HIV-1 backbone delta Env using GeneJammer. Forty-eight hours after transfection, cell supernatant was harvested and filtered through a 45 um filter.

iii. Production of Trimer

BG505_MD39-based trimers were expressed in FreeStyle 293F Cells and are derived from a low-passage Master Cell Bank and certified mycoplasma free. The trimer-containing supernants were obtained by centrifuging (4000×g, 25 mins) and filtering (0.2 um Nalgene Rapid-Flow Filter) the 293F cultures. Trimers were purified from supernants by lectin purification using lectin beads (7.5 ml beads/1 L culture) and lectin elution buffer (1M Methyl alpha-D-mannopyranoside). The elution was dialyzed overnight into PBS. The trimers were then purified over a size-exclusion chromatography column (GE S200 Increase) in PBS. The molecular weight and homogeneity of the trimers were confirmed by protein conjugated analysis from ASTRA with data collected from a size-exclusion chromatography-multi-angle light scattering (SEC-MALS) experiment run in PBS using a GE S6 Increase column followed by DAWN HELEOS II and Optilab T-rEX detectors. The trimers were aliquoted at 1 mg/ml and flash frozen in thin-walled PCR tubes prior to use.

iv. Immunization of Mice

All mice were housed in compliance with the NIH and Wistar's Institutional Animal Care and Use Committee guidelines. To test for immunogenicity, 6-8 week old BalbC mice were immunized with 25 ug of each plasmid followed by in vivo electroporation using the CELLECTA® 3P adaptive constant current electroporation device. Mice were immunized at either 0, 3, 6 or 0, 3, 16 and sacrificed one week after final immunization to assess vaccine induced immune responses. A subset of mice were given recombinant protein trimer formulated in RIBI adjuvant at a 25 ug dose delivered to two sites subq at weeks 0, 3, 6.

v. Immunization of Rabbits

All rabbits were housed and handled according to the standards of the Institutional Animal Care and Use Committee (IACUC) at BioTox Sciences (San Diego, Calif.). Female New Zealand white rabbits (1900 grams) were immunized using 1-2 mg plasmid of DNA intradermal at weeks 0, 4, 12, 20 with in vivo EP as described above. All rabbits received two injection sites. Blood was collected for analysis at weeks −2, 2, 6, 12, 14, 17, 20, 22, and 28.

vi. Immunization of Non-Human Primates

Ten rhesus macaques were housed at Bioqual (Rockville Md.) according to the standards of the American Association for Accreditation of Laboratory Animal Care, and all animal protocols were IACUC approved. All animals received four vaccinations all via the intradermal route. Half of the NHPs received 2 mg of pMD39_Gly_opt and the other half received 2 mg of the pMD39_TS1 delivered to two sites. The animals were vaccinated on weeks 0, 4, 12, 20. All DNA deliveries were followed by in vivo EP with the constant current CELLECTRA® device with three pulses at 0.5 A constant current, a 52 ms pulse length and is rest between pulses.

vii. Blood Collection

NHPs were bled at weeks −2, 2, 6, 12, 14, 20, 22, and 28. Blood (15 ml at each time point) was collected in EDTA tubes, and peripheral blood mononuclear cells (PBMCs) were isolated using the standard Ficoll-Hypaque procedure with Accuspin tubes (Sigma-Aldrich). An additional 10 ml was collected into clot tubes for serum collection.

viii. Mouse IFN-Gamma Enzyme-Linked Immunospot Assay (ELISpot)

Ninety-six well filter plates were pre-coated with anti-IFN-γ capture antibody.

Spleens were isolated from mice two week after final immunization. After processing the spleens to obtain a single cell suspension, 2×105 cells were added to the blocked plates. Cells were stimulated with overlapping 15mer peptide pools for WT BG505 gp160 (5 ug/ml per peptide). Media alone and concanavalin A were used as negative and positive controls respectively. After 18 hrs of stimulation, the plates were washed, and detection antibody (R4-6A2-biotin) was added for 2 hrs at RT. Plates were then washed and the Streptavidin-ALP antibody was added for 1 hour at RT. Plates were then developed using the BCIP/NBT-plus for 10 minutes. Plates were then scanned and counted using CTL-ImmunoSpot® S6 FluoroSpot plate reader.

ix. Intracellular Cytokine Staining

For intracellular cytokine staining, 2×106 splenocytes were stimulated in the presence of protein transport inhibitor, GolgiStop™ GolgiPlug™ with the same peptide pools as the ELISpots. Media alone and phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulations were used as negative and positive controls respectively. To test for degranulation of cells, anti-CD107a antibody was also added during stimulation. After 6 hrs, cells were washed and stained with LIVE/DEAD violet. Surface staining was then added containing anti-CD4, anti-CD8, anti-CD62L and anti-CD44. After 30 minute incubation, cells were spun, washed, and fixed using the CytoPerm CytoWash kit following manufacturer's protocol. Intracellular staining was then prepared using anti-IFNγ, anti-TNFα, anti-IL2, and anti-CD3.

All data was collected on a modified LSRII flow cytometer followed by analysis with FlowJo software.

x. ELISA

Binding titers to gp120 were determined by coating plates with 1 ug/ml of BG505 gp120 overnight in PBS. After washing, plates were blocked with 5% skim milk in PBS with 1% newborn calf serum (NBS) and 0.2% Tween for 1 hour at RT. Serum was serially diluted, added to plates and incubated at 37o for 1 hour. Antigen and species specific IgG was then detected with secondary anti-mouse, rabbit or NHP HRP antibody. Plate were developed for 5 minutes with TMB and stopped with 2N H2SO4.

Binding titers to trimer were determined by coating plates with 2 ug/ml of recombinant PGT128 antibody overnight in PBS. After washing, plates were blocked with 5% skim milk in PBS with 1% newborn calf serum (NBS) and 0.2% Tween for 1 hour at RT. Recombinant trimer was added at 4 ug/ml for 2 hours at RT. Serum was serially diluted, added to plates and incubated at 37o for 1 hour. Antigen and species specific IgG was then detected with secondary anti-mouse, rabbit or NHP HRP antibody. Plate were developed for 5 minutes with TMB and stopped with 2N H2SO4.

Competition ELISAs were performed using a similar protocol for trimer specific antibodies. Serum was diluted at a 1:60 concentration and added to plates for 1 hour at 37°. Recombinant 1 TA or 12N were then added at a set concentration to yield the EC70 binding. Competition was then determined by detecting with a secondary anti-human HRP antibody. Plate were developed for 5 minutes with TMB and stopped with 2N H2SO4. Percent competition was determined using the following equation ((1−(OD450 EC70−sample OD))*100.

xi. Neutralization Assay

Pseudotype viruses were titered to yield 1500, 000 RLU after 48 h of infection with Tzm-Bl cells. Mouse serum was heat inactivated for 15 minutes at 56° and NHP serum was inactivate for 30 minutes. Serum or monoclonal antibody controls were serially diluted and incubated with virus before adding 10,000 Tzm-Bl cells per well with dextran. Forty-eight hours after incubation, media was removed and cells were lysed using BriteLite luciferase reagent. Serum concentration/titer was determined for 50% virus neutralization (IC50).

xii. Statistics

All statistics and calculations were performed using GraphPad Prism 7.0. EC50 and EC70 concentrations were calculated using a non-linear regression model. IC50 values were computed with a non-linear regression model of percentage neutralization vs log reciprocal serum dilution. All statistical test were calculated in GraphPad using p<0.05 as significant. In most cases a modified one-way ANOVA was performed and corrected for multiple comparisons.

2. Results/Discussion

i. Protein vs DNA immunization of Trimer immunogens.

In order to first explore the ability of DNA encoded native like HIV-1 Envelope trimers, immune responses were compared in mice receiving either recombinant trimer or EP-DNA. Mice were delivered the same dose (25 ug) of either DNA or protein delivered at weeks 0, 3, and 6 (FIG. 1A). Two weeks after final immunization, mice were sacrificed and cellular responses were determined using overlapping peptides for WT BG505 Env sequence. The mice immunized with DNA alone were able to induce strong T cell responses especially compared to the recombinant protein immunized animals. These antigen specific T cells were able to recognize peptides from across the antigen (FIG. 1B) and were both CD4+ and CD8+ T cells (FIG. 1D). Additionally, both CD4+ and CD8+ antigen specific T cells were able to express multiple cytokines including triple positive cells (expressing IFN-γ, TNFα, and IL-2) (FIGS. 1C and 1E). The ability of these mice to induce antibodies which recognize the HIV-1 native like trimer were also investigated. Humoral responses were determined post dose 1, 2, and 3 and at all time points, DNA was able to induce higher binding antibodies (FIG. 2B, 2C). Two weeks after the final immunization, there was still a trend to higher binding antibodies to trimer in the DNA group, but this difference was not significant.

Previously, groups have demonstrated that through recombinant stabilized native like trimer protein can induce autologous Tier 2 neutralizing antibody titers in larger animals (rabbits and NHPS), these responses have not been observed in mice. The dogma was that though mice could induce strong binding antibodies, develop good Tfh responses and germinal centers, they did not have the BCRs to induce an autologous neutralizing antibody response. In light of this, we decided to investigate if our DNA encoded trimer was able to induce autologous neutralizing antibodies to BG505. In the naïve, pVax backbone control and protein only immunize mice, neutralizing titers were not observed against BG505 pseudotype virus. However, in 3 out of 10 (or 30%) of mice immunized with DNA no neutralizing antibody titers were observed (FIG. 2D). In all cases, no mice were able to neutralize the MLV control virus to prevent any non-specific neutralization effects.

ii. Improving the Antibody Immune Response by Increasing the Interval Between Boost.

It has been previously demonstrated that longer intervals between vaccinations can yield a superior antibody responses by allow time for somatic hypermutation and affinity maturation to occur. Lengthening the interval between the second and third immunization could increase our antibody responses. Mice were immunized with 25 ug of DNA encoding the native like trimer followed by EP at weeks 0, 3, 6 or weeks 0, 3, 16. In both regimens, mice were euthanized two weeks after final immunization. Mice immunized with the longer interval induced higher T cell responses compared to the shorter immunization schedule (FIG. 3A). In both cases, these T cells were both CD4+ and CD8+ in specificity. Interesting, the longer interval induced stronger CD4 poly-functionally (FIG. 3B) whereas the shorter immunization induce more CD8 poly-functionality (FIG. 3E). Both schedules were able to induce strong antibody responses which recognized by recombinant trimer and gp120 monomer (FIG. 4). It is important to note that there is not much of a decline in antibody titers between week 5 (2 weeks post dose 2) and week 16 (pre dose 3) for the longer interval (FIG. 4C). Extending the interval improves the neutralization responses. In the longer interval group, 7 out of 10 mice developed neutralization titers compared to 3 out of 10 for the short immunization (FIG. 5). This indicates that a longer interval improves the antibody neutralization capacity.

iii. Exploring Additional Constructs—Making Improvements

Though the pMD39-Opt construct was able to induce autologous tier 2 neutralizing antibody titers, making improvements on this construct as well as further defining which type of construct worked best for DNA plasmid delivery was investigated. Currently, MD39 relies on furin for cleavage. By including different linkers, a trimer can be encoded which is no longer dependent on furin. Additionally, immunogens can be encoded which have the bottom of the trimer masked to prevent off target bottom binding antibodies by including mutations to add in a glycan. A string of monomers (trimer strings) can also be encoded which could allow for better folding and proper assembly when multiple Envs are expressed in the same cell. Adding a transmembrane domain and physically linking the trimer to the membrane could change the immune responses.

Binding titers to gp120 and HIV-1 Env trimer were explored. Previous iterations of DNA encoded Envs, WT and gp120 foldons, were able to induce good binding titers to gp120 monomer but weak and spotty responses to trimer. When the disclosed DNA encoded trimers were used, higher binding titers to trimer and slight lower binding responses to gp120 monomer was observed (FIG. 6). There was no difference in terms of binding between any of the trimer constructs. Cellular responses of these immunogen were also explored. All mice were able to induce significantly higher antigen specific T cell responses compared to naïve mice (FIG. 7). There was a decrease in cellular responses for the trimer string antigens and the membrane bound antigens. However, all constructs were able to induce both CD4+ and CD8+ T cells.

iv. V3 Responses Induced by DNA Encoded Trimer Immunogens.

In gp120, the V3 loop is exposed and folded out. In native like trimers, this loop is buried and is not exposed to the immune system. Thus, antibodies binding to V3 can be an indirect measure of proper antigen folding. The reactivity of a subset of serum from the DNA immunized mice were explored. Compared to control gp120 foldon immunized mice, a significant decrease in the V3 binding antibodies was seen (FIG. 8). As a control, ELISAs were performed on scrambled peptides to ensure this binding was specific. Thus, the DNA encoded trimers are folding properly.

v. DNA Encoded Modifications Limit Bottom Binding Antibodies

In the pMD39-OPT construct, the base of the trimer is exposed due to secretion. Normally, in the context of infection, this region is hidden by the transmembrane region of the Env. However, this immunodominant region is exposed when it is expressed as a soluble trimer. This region can be “hidden” from the immune system by adding in different glycans, creating different linker locations or attaching it to the membrane. In order to explore if these modifications were able to prevent reactivity, a competition ELISA was performed using a known monoclonal that binds to the bottom of the trimer. Compared to base pMD39_opt, the addition of glycans, linkers or linking it to the membrane, significantly decreased the amount of antibodies that competed for binding with 12N (FIG. 9). In other words, these mice induces less bottom binding antibodies. This is an important demonstration of how different modifications encoded in DNA can translate to in vivo immune responses. Additionally it is an indirect demonstration that glycan sites can be encoded and obtain those glycosylation events.

vi. Neutralization of Autologous Tier 2 BG505 Virus

If autologous neutralizing antibody titers were induced with the different forms of DNA encoded structural immunogens was investigated. The best membrane bound immunogen was the trimer string_PDGFR that induced 50% of mice inducing autologous neutralizing titers. The soluble antigens induce between 60-70% of autologous neutralizing antibody titers. There was no neutralization with MLV control virus. Thus, across multiple antigens and different iteration we are able to get tier 2 autologous neutralizing antibody titers in mice (FIG. 10). Where these antibodies bound and neutralize the virus was determined. There is a monoclonal antibody which binds to the epitope which is dominant in rabbits immunized with a similar protein antigens. This antibody binds to a hole in the glycans on HIV Env at the 241 position. It is called 11A. A competition ELISA can be used to determine if the serum is binding to this epitope. Serum from mice immunized at wk 0, 3, 16 (wk 18 serum was used) for the competition with 1 TA. There was no competition with 11 A from the mouse serum (FIG. 11A). Mutations were made to the BG505 virus to add in a glycan at this site (S241N mutation). By adding in this mutation, 11A was prevented from neutralizing the pseudotype virus thus demonstrating that the virus is in fact glycosylated at this position. The control in this experiment is PDGM1400 which is a broadly neutralizing antibody and is able to neutralize both the parent and mutated virus to the similar extent. When using serum from mice that are able to induce neutralization titers to BG505 T332N vs those which did not, no decrease in neutralization capacity with the S241N mutation was observed, indicating that the mouse neutralizing response is not targeting this region (FIG. 11).

The next epitope tested was the C3/465 region of the Envelop. This is the dominant neutralizing epitope response in NHPs and is in 25% of rabbits. A virus was produced which encodes the T465N (adding a glycan at this position). The majority of antibody responses are removed and all are decreased in titers (FIG. 11B). Furthermore, the maternal strain (MG505) which was the transmitting virus into the baby girl (BG505) for which this initial Env sequence was isolated, is closely related (17AA differences) (FIG. 11B). One of these is in the region previously observed in NHPs (I396N). This could explain why MG505 is not neutralized by the mouse serum.

vii. Rabbits Immunized with DNA Encoded Trimers Induce Trimer Specific Binding Antibodies and Some Autologous Tier 2 Neutralizing Titers

After downselection in mice, four different DNA encoded trimers were moved into larger animal models—the rabbit. Rabbits were immunized with either 1-2 mg of DNA based on the molar amount delivered to two sites ID with CELLECTRA 3P at wk 0, 4, 12, 20 (FIG. 12). Trimer specific antibody responses were detected with complete seroconverstion post second immunization. These responses were slightly higher with pOpt-MD39 compared to the other DNA encoded immunogens. This could be due to increased bottom binding antibodies. There are some neutralization titers post third immunization against autologous virus (BG505 T332N) which are further boosted after forth immunization (FIG. 13). There was limited to no non-specific (MLV) neutralizing titers (FIG. 13).

viii. NHPs Immunized with DNA Encoded Trimers Induce Trimer Specific Binding Antibodies and Antigen Specific T Cell Responses

The ability for DNA encoded native like trimers to induce responses was also studied in NHPs. NHPs were immunized with 2 mgs of DNA delivered to two sites ID with CELLECTRA 3Pat weeks 0, 4, 12, and 20 (FIG. 14). Antigen specific T cells were observed as early as post first dose and subsequentially boosted after each immunization (FIG. 14B). Additionally, antigen specific T cells recognized the entire length of the protein as seen in responses to every peptide pool (FIG. 14C). These NHPS are able to induce stronger trimer specific antibody titers compared to gp120 specific responses post dose 2 (FIG. 15). It is too early to determine if these NHPS will develop autologous neutralizing antibody titers.

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.

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The disclosure relates to compositions, pharmaceutical compositions, and cells comprising nucleic acid molecules such as plasmids comprising at least a first expressible nucleic acid sequence that comprises any one or combination of sequences in Table Y or any one or combination of nucleic acid sequences that encode an amino acid sequence from Table Y. The disclosure relates to compositions, pharmaceutical compositions, and cells comprising fragments of those sequences or mutants of those sequences that comprise at least 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to nucleic acid sequence fragments at least 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 275, 300, 350, 400, 450, 500 or more nucleic acids of the sequence of Table Y.

In some embodiments, the disclosure relates to pharmaceutical compositions or cells comprising such pharmaceutical compositions comprising a plasmid disclosed herein with at least one expressible nucleic acid that is any one or combination of sequences in Table Y or any one or combination of nucleic acid sequences that encode an amino acid sequence from Table Y, or pharmaceutically salts thereof, or any sequence comprising at least 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to those sequences identified in Table Y.

TABLE Y of SEQUENCES

BG505 MD39 based sequences Parts of sequences Leader sequences IgE MDWTWILFLVAAATRVHS (SEQ ID NO: 7) MD39 atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattcc (SEQ ID NO: 2) CPG9.2 atggattggacttggattctgttcctggtcgcagcagccacacgagtgcatagc (SEQ ID NO: 3) Cleavage sites Furin RRRRRR (SEQ. ID NO: 236) Cggcgcaggagacggcgc (SEQ ID NO: 237) Linkers Link 14 SHSGSGGSGSGGHA (SEQ ID NO: 14) tctcacagcggctccggcggctctggcagcggcggccacgcc GS linkers (SEQ ID NO: 17) (SEQ ID N0: 15) CPG9.2 GGNSSG (SEQ ID NO: 20) Gggggaaatagtagcggc (SEQ ID NO: 18) GGNGSGGGSGSGGNGSSG (SEQ ID NO: 23) Ggcggcaacggcagcggcggcggcagcggctccggcggcaacggctctagcggc (SEQ ID NO: 21) PDGFR linker between trimer or TS1 and PDGFR GGGSGGSGGSGGSGGSGGS (SEQ ID NO: 26) Ggaggaggaagcgggggaagcgggggaagcggaggaagcgggggaagcgggggaagc (SEQ ID NO: 24) Foldon PDGFR linkers GGGSGGSGGG (SEQ ID NO: 29) Ggaggaggaagcgggggaagcggcggcggc (SEQ ID NO: 27) GGSGGSGGSGGS (SEQ ID NO: 32) Gggggaagcggaggaagcgggggaagcgggggaagc (SEQ ID NO: 29) 3BVE GSG ggaagcggc I3_1 GGSGSGGSGG (SEQ ID NO: 35) Ggcggcagcggcagcggcgggagcggagga (SEQ ID NO: 33) I3_2 GGSDMRKDAERRFDKFVEAAKNKFDKFKAALRKGDIKEERRKDMKKLARKEAEQARRAVRNRLSELLSKINDMPIT NDQKKLMSNDVLKFAAEAEKKIEALAADAEGGSGS (SEQ ID NO: 38) Ggagggagcgatatgagaaaggacgccgagagacggtttgataagttcgtggaggctgctaagaataagtttgacaagtttaaggctgccctg cggaagggcgacatcaaggaggagaggagaaaggatatgaagaagctggcaaggaaggaggcagagcaggcaaggagggccgtgaggaa cagactgagcgagctgctgtccaagatcaacgacatgcccatcaccaatgatcagaagaagctgatgtctaatgacgtgctgaagttcgccgca gaagccgaaaagaagattgaagccctggcagcagacgccgaaggaggaagcgggagc (SEQ ID NO: 36) LS_1 GGSSGKSLVDTVYALKDEVQELRQDNKKMKKSLEEEQRARKDLEKLVRKVLKNMNDGGSSG (SEQ ID NO: 41) Gggggctctagcgggaaaagtctggtggataccgtctatgctctgaaagatgaggtgcaggaactgaggcaggacaacaaaaagatgaagaa gagcctggaggaggagcagagggccagaaaggacctggaaaaactggtgcggaaagtgctgaaaaacatgaatgacggagggagtagcgg g (SEQ ID NO: 39) LS_2 GGSSGADPKKVLDKAKDQAENRVRELKQKLEELYKEARKLDLTQEMRRKLELRYIAAMLMAIGDIYNAIRQAKQEA DKLKKAGLVNSQQLDELKRRLEELKEEASRKARDYGREFQLKLEYGGGSGSGSG (SEQ ID NO: 44) Gggggctctagcggggcagacccaaagaaagtgctggataaggcaaaggatcaggcagagaatagagtgagagaactgaaacagaaactg gaggaactgtataaggaggcccggaagctggacctgacccaggagatgaggagaaagctggagctgcgctacatcgccgccatgctgatggc catcggcgacatctataacgccatcaggcaggccaagcaggaggccgataagctgaagaaggccggcctggtgaatagccagcagctggacg agctgaagcggcgcctggaggagctgaaggaggaggcctccaggaaggccagagattatgggcgggaatttcagctgaaactggagtatggc ggcggaagcggaagcgggagcggg (SEQ ID NO: 42) QB_1 GGSSGGTDVGAIAGKANEAGQGAYDAQVKNDEQDVELADHEARIKQLRIDVDDHESRITANTKAITALNVRVTTA EGEIASLQTNVSALDGRVTTAENNISALQADYVSGGSSGSG (SEQ ID NO: 47) Ggaggctcttcaggcggcacagacgtgggggcaatcgctggaaaggctaacgaggctggacagggggcttatgatgctcaggtcaaaaacga cgagcaggatgtggagctggccgaccacgaggccaggatcaagcagctgagaatcgatgtggacgatcacgagtctcggatcaccgccaaca caaaggccatcacagccctgaatgtgcgcgtgaccacagcagagggagagatcgcatccctgcagaccaacgtgagcgccctggacggaagg gtgaccacagcagagaacaatatctccgccctgcaggcagattacgtgagcggcggcagctccggctccgga (SEQ ID NO: 45) QB_2 GGSGSGGSSGPHMIAPGHRDEFDPKLPTGEKEEVPGKPGIKNPETGDVVRPPVDSVTKYGPVKGDSIVEKEEIPFEK ERKFNPDLAPGTEKVTREGQKGEKTITTPTLKNPLTGEIISKGESKEEITKDPINELTEWGPETGGSGSGGSS ggaggctctggaagcgggggaagtagcggacctcacatgattgctccaggacatcgggacgagtttgaccctaagctgccaacaggcgagaaa gaagaggtgccaggcaagcccggcatcaagaaccctgagacaggcgacgtggtgaggccccctgtggattctgtgacaaagtacggcccagtg aagggcgacagcatcgtggagaaggaggagatccccttcgagaaggagaggaagtttaaccctgatctggccccaggcaccgagaaggtgac aagagagggccagaagggcgagaagaccatcaccacacccacactgaagaatcctctgaccggcgagatcatcagcaagggcgagtccaag gaggagatcacaaaggaccccatcaacgaactgaccgaatggggaccagagacaggaggaagcggcagcggcggaagcagc IC1/IC2 GGSGSGSG (SEQ ID NO: 50) Ggaggcagcggcagcggcagcggg (SEQ ID NO: 48) Membrane bound domains PDGFR NAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKKPR (SEQ ID NO: 232) Aacgccgtgggccaggacacccaggaagtgatcgtggtgccccacagcctgcctttcaaggtggtggtcatctccgccatcctggccctggtcgt gctgactattatttccctgattatcctgattatgctgtggcagaagaagcccaga (SEQ ID NO: 230) Foldon YIPEAPRDGQAYVRKDGEWVLLSTFL (SEQ ID NO: 235) Tacatccctgaggccccaagggacggacaggcctatgtgagaaaggatggcgagtgggtgctgctgtccaccttcctg (SEQ ID NO: 233) Nanoparticle domains 3BVE (amino acid, dna, rna) GLSKDIIKLLNEQVNKEMQSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPE HKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLAD QYVKGIAKSRKS (SEQ ID NO: 135) Gggctgagtaaggacattatcaagctgctgaacgaacaggtgaacaaagagatgcagtctagcaacctgtacatgtccatgagctcctggtgct atacccactctctggacggagcaggcctgttcctgtttgatcacgccgccgaggagtacgagcacgccaagaagctgatcatcttcctgaatgag aacaatgtgcccgtgcagctgacctctatcagcgcccctgagcacaagttcgagggcctgacacagatctttcagaaggcctacgagcacgagc agcacatctccgagtctatcaacaatatcgtggaccacgccatcaagtccaaggatcacgccacattcaactttctgcagtggtacgtggccgag cagcacgaggaggaggtgctgtttaaggacatcctggataagatcgagctgatcggcaatgagaaccacgggctgtacctggcagatcagtat gtcaagggcatcgctaagtcaaggaaaagc (SEQ ID NO: 133) GGGCUGAGUAAGGACAUUAUCAAGCUGCUGAACGAACAGGUGAACAAAGAGAUGCAGUCUAGCAACCU GUACAUGUCCAUGAGCUCCUGGUGCUAUACCCACUCUCUGGACGGAGCAGGCCUGUUCCUGUUUGAUC ACGCCGCCGAGGAGUACGAGCACGCCAAGAAGCUGAUCAUCUUCCUGAAUGAGAACAAUGUGCCCGUGC AGCUGACCUCUAUCAGCGCCCCUGAGCACAAGUUCGAGGGCCUGACACAGAUCUUUCAGAAGGCCUACG AGCACGAGCAGCACAUCUCCGAGUCUAUCAACAAUAUCGUGGACCACGCCAUCAAGUCCAAGGAUCACGC CACAUUCAACUUUCUGCAGUGGUACGUGGCCGAGCAGCACGAGGAGGAGGUGCUGUUUAAGGACAUCC UGGAUAAGAUCGAGCUGAUCGGCAAUGAGAACCACGGGCUGUACCUGGCAGAUCAGUAUGUCAAGGGC AUCGCUAAGUCAAGGAAAAGC (SEQ ID NO: 134) I3 (amino acid, dna, rna) MKMEELFKKHKIVAVLRANSVEEAKKKALAVFLGGVHLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQCRK AVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFV PTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPVEVAEKAKAFVEKIRGCTE (SEQ ID NO: 138) Atgaagatggaagaactgttcaagaagcacaagatcgtggccgtgctgagggccaactccgtggaggaggccaagaagaaggccctggccgt gttcctgggcggcgtgcacctgatcgagatcacctttacagtgcccgacgccgataccgtgatcaaggagctgtctttcctgaaggagatgggag caatcatcggagcaggaaccgtgacaagcgtggagcagtgcagaaaggccgtggagagcggcgccgagtttatcgtgtcccctcacctggacg aggagatctctcagttctgtaaggagaagggcgtgttttacatgccaggcgtgatgacccccacagagctggtgaaggccatgaagctgggcca cacaatcctgaagctgttccctggcgaggtggtgggcccacagtttgtgaaggccatgaagggccccttccctaatgtgaagtttgtgcccaccg gcggcgtgaacctggataacgtgtgcgagtggttcaaggcaggcgtgctggcagtgggcgtgggcagcgccctggtgaagggcacacccgtgg aagtcgctgagaaggcaaaggcattcgtggaaaagattagggggtgtactgag (SEQ ID NO: 136) AUGAAGAUGGAAGAACUGUUCAAGAAGCACAAGAUCGUGGCCGUGCUGAGGGCCAACUCCGUGGAGGA GGCCAAGAAGAAGGCCCUGGCCGUGUUCCUGGGCGGCGUGCACCUGAUCGAGAUCACCUUUACAGUGCC CGACGCCGAUACCGUGAUCAAGGAGCUGUCUUUCCUGAAGGAGAUGGGAGCAAUCAUCGGAGCAGGAA CCGUGACAAGCGUGGAGCAGUGCAGAAAGGCCGUGGAGAGCGGCGCCGAGUUUAUCGUGUCCCCUCACC UGGACGAGGAGAUCUCUCAGUUCUGUAAGGAGAAGGGCGUGUUUUACAUGCCAGGCGUGAUGACCCCC ACAGAGCUGGUGAAGGCCAUGAAGCUGGGCCACACAAUCCUGAAGCUGUUCCCUGGCGAGGUGGUGGG CCCACAGUUUGUGAAGGCCAUGAAGGGCCCCUUCCCUAAUGUGAAGUUUGUGCCCACCGGCGGCGUGAA CCUGGAUAACGUGUGCGAGUGGUUCAAGGCAGGCGUGCUGGCAGUGGGCGUGGGCAGCGCCCUGGUG AAGGGCACACCCGUGGAAGUCGCUGAGAAGGCAAAGGCAUUCGUGGAAAAGAUUAGGGGGUGUACUGA G (SEQ ID NO: 137) LS (amino acid, dna, rna)

Atgcagatctacgaaggaaaactgaccgctgagggactgaggttcggaattgtcgcaagccgcgcgaatcacgcactggtggataggctggtg gaaggcgctatcgacgcaattgtccggcacggcgggagagaggaagacatcacactggtgagagtctgcggcagctgggagattcccgtggca gctggagaactggctcgaaaggaggacatcgatgccgtgatcgctattggggtcctgtgccgaggagcaactcccagcttcgactacatcgcctc agaagtgagcaaggggctggctgatctgtccctggagctgaggaaacctatcacttttggcgtgattactgccgacaccctggaacaggcaatc gaggcggccggcacctgccatggaaacaaaggctgggaagcagccctgtgcgctattgagatggcaaatctgttcaaatctctgcga (SEQ ID NO: 139)

QB (amino acid, dna, rna) AKLETVTLGNIGKDGKQTLVLNPRGVNPTNGVASLSQAGAVPALEKRVTVSVSQPSRNRKNYKVQVKIQNPTACT ANGSCDPSVTRQAYADVTFSFTQYSTDEERAFVRTELAALLASPLLIDAIDQLNPAY (SEQ ID NO: 144) Gcaaagctggagacagtgacactgggcaacatcggcaaggacggcaagcagacactggtgctgaatcccaggggcgtgaaccctaccaatg gagtggcatctctgagccaggcaggagcagtgcctgccctggagaagagagtgaccgtgtccgtgtctcagcccagcaggaacagaaagaatt ataaggtgcaggtgaagatccagaacccaaccgcctgcacagccaatggcagctgtgacccatccgtgacaaggcaggcatacgcagatgtga ccttctcttttacacagtatagcaccgatgaggagagggccttcgtgcgcaccgagctggccgccctgctggcatcccctctgctgattgacg ctattgaccagctgaaccctgcttac (SEQ ID NO: 142) GCAAAGCUGGAGACAGUGACACUGGGCAACAUCGGCAAGGACGGCAAGCAGACACUGGUGCUGAAUCCC AGGGGCGUGAACCCUACCAAUGGAGUGGCAUCUCUGAGCCAGGCAGGAGCAGUGCCUGCCCUGGAGAA GAGAGUGACCGUGUCCGUGUCUCAGCCCAGCAGGAACAGAAAGAAUUAUAAGGUGCAGGUGAAGAUCC AGAACCCAACCGCCUGCACAGCCAAUGGCAGCUGUGACCCAUCCGUGACAAGGCAGGCAUACGCAGAUGU GACCUUCUCUUUUACACAGUAUAGCACCGAUGAGGAGAGGGCCUUCGUGCGCACCGAGCUGGCCGCCCU GCUGGCAUCCCCUCUGCUGAUUGACGCUAUUGACCAGCUGAACCCUGCUUAC (SEQ ID NO: 143) IC1 (amino acid, dna, rna) DPEFTKNALNVVKNDLIAKVDQLSGEQEVLRGELEAAKQAKVKLENRIKELEEELKRV (SEQ ID NO: 147) Gaccctgagtttaccaaaaatgctctgaatgtcgtcaaaaatgatctgattgctaaggtggaccagctgagcggagagcaggaggtgctgagg ggcgagctggaggccgccaagcaggcaaaggtgaaactggaaaaccgaatcaaggaactggaagaagaactgaaaagagtc (SEQ ID NO: 145) GACCCUGAGUUUACCAAAAAUGCUCUGAAUGUCGUCAAAAAUGAUCUGAUUGCUAAGGUGGACCAGCU GAGCGGAGAGCAGGAGGUGCUGAGGGGCGAGCUGGAGGCCGCCAAGCAGGCAAAGGUGAAACUGGAAA ACCGAAUCAAGGAACUGGAAGAAGAACUGAAAAGAGUC (SEQ ID NO: 146) IC2 (amino acid, dna, rna) ADPKKVLDKAKDQAENRVRELKQKLEELYKEARKLDLTQEMRRKLELRYIAAMLMAIGDIYNAIRQAKQEADKLKK AGLVNSQQLDELKRRLEELKEEASRKARDYGREFQLKLEYGGGSGSGSGGKIEQILQKIEKILQKIEWILQKIEQILQG (SEQ ID NO: 150) Gccgaccccaagaaggtgctggataaagccaaagatcaggcagaaaatagagtcagggaactgaagcagaagctggaggagctgtacaag gaggcccggaagctggacctgacccaggagatgaggagaaagctggagctgcgctacatcgccgccatgctgatggccatcggcgacatctat aacgccatcaggcaggccaagcaggaggccgataagctgaagaaggccggcctggtgaatagccagcagctggacgagctgaagcggcgcc tggaggagctgaaggaggaggccagcaggaaggccagagattacggcagggagttccagctgaagctggagtatggcggcggcagcggctc cggctctggcggcaagatcgagcagatcctgcagaagatcgaaaagatcctgcagaagattgagtggattctgcagaagattgaacagatcct gcagggg (SEQ ID NO: 148) GCCGACCCCAAGAAGGUGCUGGAUAAAGCCAAAGAUCAGGCAGAAAAUAGAGUCAGGGAACUGAAGCAG AAGCUGGAGGAGCUGUACAAGGAGGCCCGGAAGCUGGACCUGACCCAGGAGAUGAGGAGAAAGCUGGA GCUGCGCUACAUCGCCGCCAUGCUGAUGGCCAUCGGCGACAUCUAUAACGCCAUCAGGCAGGCCAAGCA GGAGGCCGAUAAGCUGAAGAAGGCCGGCCUGGUGAAUAGCCAGCAGCUGGACGAGCUGAAGCGGCGCC UGGAGGAGCUGAAGGAGGAGGCCAGCAGGAAGGCCAGAGAUUACGGCAGGGAGUUCCAGCUGAAGCUG GAGUAUGGCGGCGGCAGCGGCUCCGGCUCUGGCGGCAAGAUCGAGCAGAUCCUGCAGAAGAUCGAAAA GAUCCUGCAGAAGAUUGAGUGGAUUCUGCAGAAGAUUGAACAGAUCCUGCAGGGG (SEQ ID NO: 149) Env sections MD39 gp120 (amino acid, dna, rna) same for MD39, GRSF, link14, Trimer strings 1, Trimer strings 2, MD39_link14_PDGFR, MD39_link14_gp140_Foldon_PDGFR AENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVE QMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINE NQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVS TQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKA TWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDS ITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVV KIEPLGVAPTRCKRRVVG (SEQ ID NO: 55) gccgaaaacctgtgggtcaccgtctactatggagtgcccgtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacg agacagagaagcacaacgtgtgggcaacccacgcatgcgtgcctacagacccaaacccccaggagatccacctggagaatgtgacagaggag tttaacatgtggaagaacaatatggtggagcagatgcacgaggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccc tctgtgcgtgacactgcagtgtaccaacgtgacaaacaatatcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccaca gagctgagggacaagaagcagaaggtgtactccctgttttatagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaata gcaacaaggagtaccgcctgatcaattgcaacacctccgccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcg ccccagccggcttcgccatcctgaagtgtaaggataagaagtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggc atcaagcctgtggtgtctacacagctgctgctgaatggcagcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgcca agaatatcctggtgcagctgaacacaccagtgcagatcaattgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggcca ggccttttactataccggcgacatcatcggcgatatcagacaggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtg gtgaagcagctgaggaagcacttcggcaataacaccatcatcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttca attgcggcggcgagttcttttactgtaacacaagcggcctgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggca gcaacgattccatcacactgccatgccggatcaagcagatcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccaggg cgtgatcagatgcgtgagcaatatcaccggcctgatcctgacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcgg cggcgacatgagggataactggagatctgagctgtacaagtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagag gagagtggtgggc (SEQ ID NO: 53) GCCGAAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUU CUGCGCCAGCGAUGCCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCC UACAGACCCAAACCCCCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAA UAUGGUGGAGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGC UGACCCCUCUGUGCGUGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCG AGCUGAAGAAUUGUAGCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUG UUUUAUAGACUGGAUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGA GUACCGCCUGAUCAAUUGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAU CCCAAUCCACUAUUGCGCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAAC CGGACCAUGCCCUUCCGUGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCU GCUGCUGAAUGGCAGCCUGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAA GAAUAUCCUGGUGCAGCUGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAA GUCUAUCCGCAUCGGCCCAGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGC CCACUGUAAUGUGAGCAAGGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGC ACUUCGGCAAUAACACCAUCAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACU CCUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCC AACACAUCUGUGCAGGGCAGCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGC AGAUCAUCAACAUGUGGCAGCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAU GCGUGAGCAAUAUCACCGGCCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUU CCGGCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGA UCGAGCCUCUGGGAGUGGCACCAACCAGGUGCAAGAGGAGAGUGGUGGGC (SEQ ID NO: 54) gp120 for CPG9.2 (amino acid, dna, rna) LWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQM HEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQ GNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQ LLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATW NETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITL PCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIE PLGVAPTRCNRS (SEQ ID NO: 58) ctgtgggtgaccgtgtactatggcgtgcccgtgtggaaggacgccgagactacgctgttctgcgcctccgatgccaaggcctatgagacagaga agcacaacgtgtgggcaacccacgcatgcgtgccaacagaccctaacccacaggagatccacctggagaatgtgaccgaggagtttaacatgt ggaagaacaatatggtggagcagatgcacgaggacatcatcagcctgtgggatcagtccctgaagccttgcgtgaagctgaccccactgtgcgt gacactgcagtgtaccaacgtgacaaacaatatcaccgacgatatgaggggcgagctgaagaattgttctttcaacatgaccacagagctgag ggacaagaagcagaaagtgtacagcctgttttatagactggatgtggtgcagatcaatgagaaccagggcaataggagcaacaattccaacaa ggagtacagactgatcaattgcaacaccagcgccatcacacaggcctgtccaaaggtgtccttcgagcccatccctatccactattgcgcaccag caggattcgcaatcctgaagtgtaaggataagaagtttaacggaaccggaccatgcccatctgtgagcaccgtgcagtgtacacacggcatcaa gccagtggtgtccacacagctgctgctgaatggctctctggccgaggaggaagtgatcatccggagcgagaacatcaccaacaatgccaagaa tatcctggtgcagctgaacacacccgtgcagatcaattgcacccggcctaacaataacacagtgaagtccatcaggatcggaccaggacaggc cttttactataccggcgacatcatcggcgatatccgccaggcccactgtaacgtgagcaaggccacctggaacgagacactgggcaaggtggtg aagcagctgaggaagcacttcggcaataacaccatcatcagatttgcacagtcctctggcggcgacctggaggtgaccacacactccttcaact gcggcggcgagttcttttactgtaacacatctggcctgtttaatagcacctggatctctaacacaagcgtgcagggctccaattctaccggctcca acgattctatcacactgccctgccggatcaagcagatcatcaacatgtggcagaggatcggacaggcaatgtacgcccctcccatccagggcgt gatcagatgcgtgagcaatatcaccggcctgatcctgacacgcgacggcggcagcaccaactccaccacagagacattcagacccggcggcgg cgacatgagggataactggagatccgagctgtataagtataaagtcgtgaagattgagccactgggcgtcgcaccaacaagatgtaatagaag c (SEQ ID NO: 56) CUGUGGGUGACCGUGUACUAUGGCGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCUC CGAUGCCAAGGCCUAUGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCAACAGACCCU AACCCACAGGAGAUCCACCUGGAGAAUGUGACCGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGA GCAGAUGCACGAGGACAUCAUCAGCCUGUGGGAUCAGUCCCUGAAGCCUUGCGUGAAGCUGACCCCACU GUGCGUGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGAGGGGCGAGCUGAAGAA UUGUUCUUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAAGUGUACAGCCUGUUUUAUAGAC UGGAUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUAGGAGCAACAAUUCCAACAAGGAGUACAGACUG AUCAAUUGCAACACCAGCGCCAUCACACAGGCCUGUCCAAAGGUGUCCUUCGAGCCCAUCCCUAUCCACU AUUGCGCACCAGCAGGAUUCGCAAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCC CAUCUGUGAGCACCGUGCAGUGUACACACGGCAUCAAGCCAGUGGUGUCCACACAGCUGCUGCUGAAUG GCUCUCUGGCCGAGGAGGAAGUGAUCAUCCGGAGCGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGG UGCAGCUGAACACACCCGUGCAGAUCAAUUGCACCCGGCCUAACAAUAACACAGUGAAGUCCAUCAGGAU CGGACCAGGACAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCCGCCAGGCCCACUGUAACGU GAGCAAGGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAA CACCAUCAUCAGAUUUGCACAGUCCUCUGGCGGCGACCUGGAGGUGACCACACACUCCUUCAACUGCGG CGGCGAGUUCUUUUACUGUAACACAUCUGGCCUGUUUAAUAGCACCUGGAUCUCUAACACAAGCGUGC AGGGCUCCAAUUCUACCGGCUCCAACGAUUCUAUCACACUGCCCUGCCGGAUCAAGCAGAUCAUCAACAU GUGGCAGAGGAUCGGACAGGCAAUGUACGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAU CACCGGCCUGAUCCUGACACGCGACGGCGGCAGCACCAACUCCACCACAGAGACAUUCAGACCCGGCGGC GGCGACAUGAGGGAUAACUGGAGAUCCGAGCUGUAUAAGUAUAAAGUCGUGAAGAUUGAGCCACUGGG CGUCGCACCAACAAGAUGUAAUAGAAGC (SEQ ID NO: 57) MD39 gp41 ecto (amino acid, dna, rna) same for BG505 MD39 link 14, MD39_PDGFR AVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEH YLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQD LLALD (SEQ ID NO: 80) Gcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccagg aatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatc aagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgct gtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctcc aactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggat (SEQ ID NO: 78) GCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUC UAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAG AGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUG CUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAU CUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUA UGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAA UCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAU (SEQ ID NO: 79) BG505_MD39 GRSF gp41 ecto (amino acid, dna, rna) glycan sites added (underline) AVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEH YLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLNWSKEISNYTQIIYGLLEESQNQQEKNNQS LLALD (SEQ ID NO: 83) Gcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccagg aatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatc aagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgct gtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgaactggagcaaggagatctc caactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaataaccagagcctgctggcactggat (SEQ ID NO: 81) GCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUC UAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAG AGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUG CUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAU CUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUA UGACCUGGCUGAACUGGAGCAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAU CUCAGAAUCAGCAGGAAAAGAAUAACCAGAGCCUGCUGGCACUGGAU (SEQ ID NO: 82) BG505_MD39 CPG9.2 gp41 ecto (amino acid, dna, rna) SLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQL LGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLNWSKEISNYTQIIYGLLEESQNQNESNEQDL (SEQ ID NO: 86) Agcctggggttcctgggagcagcaggctccaccatgggagcagcatctatgaccctgacagtgcaggccaggaatctgctgtctggcatcgtgc agcagcagagcaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagctgcaggcccgggtg ctggcagtggagcactacctgcgcgatcagcagctgctgggaatctggggatgcagcggcaagctgatctgctgtacaaatgtgccttggaaca gctcctggtccaataggaacctgtctgagatctgggacaatatgacctggctgaactggtctaaggagatcagcaattacacacagatcatctat ggcctgctggaggagagccagaatcagaacgagtccaatgagcaggatctg (SEQ ID NO: 84) AGCCUGGGGUUCCUGGGAGCAGCAGGCUCCACCAUGGGAGCAGCAUCUAUGACCCUGACAGUGCAGGCC AGGAAUCUGCUGUCUGGCAUCGUGCAGCAGCAGAGCAACCUGCUGAGAGCCCCAGAGCCCCAGCAGCACC UGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAGUGGAGCACUACCUGC GCGAUCAGCAGCUGCUGGGAAUCUGGGGAUGCAGCGGCAAGCUGAUCUGCUGUACAAAUGUGCCUUGG AACAGCUCCUGGUCCAAUAGGAACCUGUCUGAGAUCUGGGACAAUAUGACCUGGCUGAACUGGUCUAA GGAGAUCAGCAAUUACACACAGAUCAUCUAUGGCCUGCUGGAGGAGAGCCAGAAUCAGAACGAGUCCAA UGAGCAGGAUCUG (SEQ ID NO: 85) BG505 full length sequences Soluble BG505 MD39 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD** (SEQ ID NO: 108) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccgtg tggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggattgataa (SEQ ID NO: 106) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 105) BG505 MD39 GRSF (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKWKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWL N W S KEISNYTQIIYGLLEESQNQQEKN N Q S LLALD** (SEQ ID NO: 111) (bold underline are mutations for glycosylation sites added) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccgtg tggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgaactggagcaaggagatctccaactac acacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaataaccagagcctgctggcactggattgataa (SEQ ID NO: 109) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGAACUGG AGCAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUAACCAGAGCCUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 110) BG505 MD39 Link 14 (amino acid, dna, rna) (cleavage independent) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD** (SEQ ID NO: 114) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccgtg tggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggattgataa (SEQ ID NO: 112) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCC ACGCCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCA GCCUCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUG CUGAGAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCA GGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAG CUGAUCUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGA CAAUAUGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGA AGAAUCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 113) BG505 MD39_CPG9.2 (amino acid, dna, rna) MDWTWILFLVAAATRVHSGGNSSGSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLK DTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLNWSKEISNYTQ IIYGLLEESQNQNESNEQDLGGNGSGGGSGSGGNGSSGLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVW ATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDM RGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAP AGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRP NNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFN CGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTR DGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCNRS** (SEQ ID NO: 117) atggattggacttggattctgttcctggtcgcagcagccacacgagtgcatagcgggggaaatagtagcggcagcctggggttcctgggagcag caggctccaccatgggagcagcatctatgaccctgacagtgcaggccaggaatctgctgtctggcatcgtgcagcagcagagcaacctgctgag agccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagctgcaggcccgggtgctggcagtggagcactacctgcg cgatcagcagctgctgggaatctggggatgcagcggcaagctgatctgctgtacaaatgtgccttggaacagctcctggtccaataggaacctgt ctgagatctgggacaatatgacctggctgaactggtctaaggagatcagcaattacacacagatcatctatggcctgctggaggagagccagaa tcagaacgagtccaatgagcaggatctgggcggcaacggcagcggcggcggcagcggctccggcggcaacggctctagcggcctgtgggtga ccgtgtactatggcgtgcccgtgtggaaggacgccgagactacgctgttctgcgcctccgatgccaaggcctatgagacagagaagcacaacgt gtgggcaacccacgcatgcgtgccaacagaccctaacccacaggagatccacctggagaatgtgaccgaggagtttaacatgtggaagaaca atatggtggagcagatgcacgaggacatcatcagcctgtgggatcagtccctgaagccttgcgtgaagctgaccccactgtgcgtgacactgca gtgtaccaacgtgacaaacaatatcaccgacgatatgaggggcgagctgaagaattgttctttcaacatgaccacagagctgagggacaagaa gcagaaagtgtacagcctgttttatagactggatgtggtgcagatcaatgagaaccagggcaataggagcaacaattccaacaaggagtacag actgatcaattgcaacaccagcgccatcacacaggcctgtccaaaggtgtccttcgagcccatccctatccactattgcgcaccagcaggattcg caatcctgaagtgtaaggataagaagtttaacggaaccggaccatgcccatctgtgagcaccgtgcagtgtacacacggcatcaagccagtggt gtccacacagctgctgctgaatggctctctggccgaggaggaagtgatcatccggagcgagaacatcaccaacaatgccaagaatatcctggtg cagctgaacacacccgtgcagatcaattgcacccggcctaacaataacacagtgaagtccatcaggatcggaccaggacaggccttttactata ccggcgacatcatcggcgatatccgccaggcccactgtaacgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctg aggaagcacttcggcaataacaccatcatcagatttgcacagtcctctggcggcgacctggaggtgaccacacactccttcaactgcggcggcg agttcttttactgtaacacatctggcctgtttaatagcacctggatctctaacacaagcgtgcagggctccaattctaccggctccaacgattcta tcacactgccctgccggatcaagcagatcatcaacatgtggcagaggatcggacaggcaatgtacgcccctcccatccagggcgtgatcagatgc gtgagcaatatcaccggcctgatcctgacacgcgacggcggcagcaccaactccaccacagagacattcagacccggcggcggcgacatgag ggataactggagatccgagctgtataagtataaagtcgtgaagattgagccactgggcgtcgcaccaacaagatgtaatagaagctgataa (SEQ ID NO: 115) AUGGAUUGGACUUGGAUUCUGUUCCUGGUCGCAGCAGCCACACGAGUGCAUAGCGGGGGAAAUAGUAG CGGCAGCCUGGGGUUCCUGGGAGCAGCAGGCUCCACCAUGGGAGCAGCAUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGUCUGGCAUCGUGCAGCAGCAGAGCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAGUGGAGCACUA CCUGCGCGAUCAGCAGCUGCUGGGAAUCUGGGGAUGCAGCGGCAAGCUGAUCUGCUGUACAAAUGUGC CUUGGAACAGCUCCUGGUCCAAUAGGAACCUGUCUGAGAUCUGGGACAAUAUGACCUGGCUGAACUGG UCUAAGGAGAUCAGCAAUUACACACAGAUCAUCUAUGGCCUGCUGGAGGAGAGCCAGAAUCAGAACGAG UCCAAUGAGCAGGAUCUGGGCGGCAACGGCAGCGGCGGCGGCAGCGGCUCCGGCGGCAACGGCUCUAGC GGCCUGUGGGUGACCGUGUACUAUGGCGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGC CUCCGAUGCCAAGGCCUAUGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCAACAGAC CCUAACCCACAGGAGAUCCACCUGGAGAAUGUGACCGAGGAGUUUAACAUGUGGAAGAACAAUAUGGU GGAGCAGAUGCACGAGGACAUCAUCAGCCUGUGGGAUCAGUCCCUGAAGCCUUGCGUGAAGCUGACCCC ACUGUGCGUGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGAGGGGCGAGCUGAA GAAUUGUUCUUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAAGUGUACAGCCUGUUUUAUA GACUGGAUGUGGUGCAGAUCAAUGAGAACCAGGGCAAUAGGAGCAACAAUUCCAACAAGGAGUACAGAC UGAUCAAUUGCAACACCAGCGCCAUCACACAGGCCUGUCCAAAGGUGUCCUUCGAGCCCAUCCCUAUCCA CUAUUGCGCACCAGCAGGAUUCGCAAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAU GCCCAUCUGUGAGCACCGUGCAGUGUACACACGGCAUCAAGCCAGUGGUGUCCACACAGCUGCUGCUGA AUGGCUCUCUGGCCGAGGAGGAAGUGAUCAUCCGGAGCGAGAACAUCACCAACAAUGCCAAGAAUAUCC UGGUGCAGCUGAACACACCCGUGCAGAUCAAUUGCACCCGGCCUAACAAUAACACAGUGAAGUCCAUCA GGAUCGGACCAGGACAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCCGCCAGGCCCACUGUA ACGUGAGCAAGGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCA AUAACACCAUCAUCAGAUUUGCACAGUCCUCUGGCGGCGACCUGGAGGUGACCACACACUCCUUCAACU GCGGCGGCGAGUUCUUUUACUGUAACACAUCUGGCCUGUUUAAUAGCACCUGGAUCUCUAACACAAGC GUGCAGGGCUCCAAUUCUACCGGCUCCAACGAUUCUAUCACACUGCCCUGCCGGAUCAAGCAGAUCAUC AACAUGUGGCAGAGGAUCGGACAGGCAAUGUACGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGC AAUAUCACCGGCCUGAUCCUGACACGCGACGGCGGCAGCACCAACUCCACCACAGAGACAUUCAGACCCG GCGGCGGCGACAUGAGGGAUAACUGGAGAUCCGAGCUGUAUAAGUAUAAAGUCGUGAAGAUUGAGCCA CUGGGCGUCGCACCAACAAGAUGUAAUAGAAGCUGAUAA (SEQ ID NO: 116) BG505 MD39_TS 1 (amino acid, dna, rna) There were different codon optimizations for each of the repeats Repeat 1: human Repeat 2: human/mouse Repeat 3: mouse MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVW KDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKP CVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLI NCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRS ENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRK HFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQR IGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVV GSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTH WGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIY GLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNM TTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKK FNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGP GQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTS GLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTET FRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMG AASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCT NVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD** (SEQ ID NO: 120) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccgtg tggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggatggcggcgccgaaaacctgtgggtcaccgtgtactacggagtccccgtgtggaaagatgcagagacaaccctgttctgcgcttccgac gctaaagcttacgagacagaaaaacacaacgtgtgggccactcatgcctgcgtgcctacagaccctaacccacaggaaatccacctggagaat gtgacggaggagtttaacatgtggaagaataacatggtcgagcagatgcatgaagatatcatttccttatgggaccaatccctgaagccttgcgt gaagctgaccccactgtgcgtgacactgcaatgcactaacgtgaccaataacattaccgacgatatgcgcggcgagctgaagaactgctctttc aacatgactaccgagctgagagataagaaacagaaagtgtacagcctgttttatcggttagatgtggtgcagatcaatgaaaaccagggcaat cggtccaacaattctaacaaggaatatcgcctgatcaattgtaacacctccgccattacccaggcttgccctaaggtgtctttcgagcccatccct atccactattgcgccccagctggatttgctatcctgaagtgtaaggacaaaaagtttaacgggaccggaccatgtcctagcgtgtccactgtgca gtgcacccatggcatcaagcctgtggtgtccacccaacttctgctgaatggctctctggctgaagaagaagtgatcattaggtccgaaaatattac taataacgctaaaaatatcctggtccagctgaacacgcctgtccagatcaattgtacccggccaaataacaacacagtgaagtctatcagaatc ggcccaggccaggccttctactacacaggcgacattatcggcgatattcgccaggcccactgtaatgtgagcaaagctacatggaatgagacac tgggcaaggtagtcaaacagctgagaaaacattttggaaacaacaccatcatccgctttgcacagtctagcggcggcgacctggaggtaactac ccacagcttcaattgtggcggcgagttcttttactgtaataccagcggcctgtttaatagtacttggatcagcaacacatctgtgcagggctctaa ctccactggctctaacgatagcatcacactgccttgtcggatcaagcaaatcatcaacatgtggcaaaggattgggcaggctatgtatgcccctcc aatccagggcgtgatccggtgcgtgagcaacattacaggcctgatcctgacaagagacggcggctccaccaactctactaccgagacattccgg cccggcggcggcgacatgcgtgataactggcgcagcgaactgtataaatataaagtggtgaagatcgagcctctgggcgtggccccaactaggt gtaaaagaagggtcgtcggctcccacagcggcagcggcggctccggctctggcggccacgcggctgtcggcatcggcgccgtgagcctgggctt tctgggcgccgccggctccactatgggcgcagcctctatgaccctgactgtccaggctagaaatctgctgtctggaatcgtgcagcagcagtcta acctgctgagggcacctgagccacaacagcacctgctgaaggatacacattggggcatcaagcagttacaagccagggtgctggccgtggaac actacctgcgcgatcagcaattactgggcatttggggatgctctggcaagctgatttgttgcaccaatgtgccctggaactcctcttggagcaaca gaaacctgtccgaaatctgggataacatgacatggctgcagtgggacaaggaaatttccaattatacccagatcatctatggactgctggaaga aagtcagaatcagcaggagaagaatgaacaggatctgctggcactggatggcggcgccgaaaacctgtgggtcaccgtgtattatggagtgcc agtgtggaaggacgccgagaccacactgttttgtgcctctgatgccaaggcctacgagaccgagaagcacaacgtgtgggccacccacgcctgc gtgcccacagacccaaatcctcaggagatccacctggagaacgtgaccgaggagtttaacatgtggaagaacaatatggtggagcagatgcac gaggatatcatctctctgtgggatcagtctctgaagccatgtgtgaagctgaccccactgtgcgtgaccctgcagtgtacaaatgtgacaaacaa catcacagatgacatgagaggcgagctgaagaactgttccttcaatatgaccaccgagctgagagacaagaagcagaaggtgtattctctgttt taccggctggacgtggtgcagatcaacgagaatcagggcaatcggtctaacaactccaataaggagtatagactgatcaactgcaacacctctg ccatcacccaggcctgtcctaaggtgtcctttgagccaatcccaatccactattgcgcccctgccggctttgccatcctgaagtgcaaggacaaga agtttaacggcacaggcccctgcccatccgtgagcacagtgcagtgtacccacggcatcaagcctgtggtgtccacccagctgctgctgaacggc tccctggccgaggaggaggtaatcatcaggtctgagaacatcacaaataacgccaagaacatcctggtgcagctgaacaccccagtgcagatc aactgtacccggcctaacaataataccgtgaagtctatccggatcggcccaggccaggccttctactataccggcgatatcatcggcgatatcag acaggcccactgcaacgtgtccaaggccacatggaacgagacactgggcaaggtggtgaagcagctgcggaagcactttggcaataacacca tcatcagattcgcccagtcttccggcggcgacctggaggtgacaacccactccttcaattgcggcggcgagttcttttactgtaatacaagcggcc tgtttaatagcacctggatctctaacacctccgtgcagggctccaacagcacaggctctaatgattccatcaccctgccttgccggatcaagcaga tcatcaatatgtggcagagaatcggccaggccatgtatgcccctccaatccagggcgtgatccgctgcgtgtccaacatcacaggcctgatcctg acaagagatggcggctccaccaacagcaccacagagaccttcagacccggcggcggcgacatgcgcgacaactggagatccgagctgtataa gtacaaggtggtgaagatcgagcccctgggcgtggccccaacccggtgtaagcgcagagtggtgggcagccacagcggcagcggcggcagcg gctccggcggccacgccgccgtgggcatcggcgccgtgtccctgggcttcctgggcgccgccggctccaccatgggcgccgcctccatgacactg acagtgcaggccagaaatctgctgtccggcatcgtgcagcagcagtccaatctgctgcgggcccctgagccacagcagcacctgctgaaggata cccactggggcatcaagcagctgcaggcccgggtgctggccgtggagcactacctgagggatcagcagctgctgggcatctggggctgttccgg caagctgatctgctgtacaaacgtgccctggaacagctcctggtccaataggaacctgtccgagatctgggataacatgacctggctgcagtggg ataaggagatcagcaactacacacagatcatctacggcctgctggaggagagccagaatcagcaggagaagaacgagcaggacctgctggcc ctggattgataa (SEQ ID NO: 118) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCC ACGCCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCA GCCUCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUG CUGAGAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCA GGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAG CUGAUCUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGA CAAUAUGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGA AGAAUCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGCGCCGAAAACCU GUGGGUCACCGUGUACUACGGAGUCCCCGUGUGGAAAGAUGCAGAGACAACCCUGUUCUGCGCUUCCG ACGCUAAAGCUUACGAGACAGAAAAACACAACGUGUGGGCCACUCAUGCCUGCGUGCCUACAGACCCUAA CCCACAGGAAAUCCACCUGGAGAAUGUGACGGAGGAGUUUAACAUGUGGAAGAAUAACAUGGUCGAGC AGAUGCAUGAAGAUAUCAUUUCCUUAUGGGACCAAUCCCUGAAGCCUUGCGUGAAGCUGACCCCACUGU GCGUGACACUGCAAUGCACUAACGUGACCAAUAACAUUACCGACGAUAUGCGCGGCGAGCUGAAGAACU GCUCUUUCAACAUGACUACCGAGCUGAGAGAUAAGAAACAGAAAGUGUACAGCCUGUUUUAUCGGUUA GAUGUGGUGCAGAUCAAUGAAAACCAGGGCAAUCGGUCCAACAAUUCUAACAAGGAAUAUCGCCUGAUC AAUUGUAACACCUCCGCCAUUACCCAGGCUUGCCCUAAGGUGUCUUUCGAGCCCAUCCCUAUCCACUAU UGCGCCCCAGCUGGAUUUGCUAUCCUGAAGUGUAAGGACAAAAAGUUUAACGGGACCGGACCAUGUCC UAGCGUGUCCACUGUGCAGUGCACCCAUGGCAUCAAGCCUGUGGUGUCCACCCAACUUCUGCUGAAUGG CUCUCUGGCUGAAGAAGAAGUGAUCAUUAGGUCCGAAAAUAUUACUAAUAACGCUAAAAAUAUCCUGG UCCAGCUGAACACGCCUGUCCAGAUCAAUUGUACCCGGCCAAAUAACAACACAGUGAAGUCUAUCAGAA UCGGCCCAGGCCAGGCCUUCUACUACACAGGCGACAUUAUCGGCGAUAUUCGCCAGGCCCACUGUAAUG UGAGCAAAGCUACAUGGAAUGAGACACUGGGCAAGGUAGUCAAACAGCUGAGAAAACAUUUUGGAAAC AACACCAUCAUCCGCUUUGCACAGUCUAGCGGCGGCGACCUGGAGGUAACUACCCACAGCUUCAAUUGU GGCGGCGAGUUCUUUUACUGUAAUACCAGCGGCCUGUUUAAUAGUACUUGGAUCAGCAACACAUCUGU GCAGGGCUCUAACUCCACUGGCUCUAACGAUAGCAUCACACUGCCUUGUCGGAUCAAGCAAAUCAUCAA CAUGUGGCAAAGGAUUGGGCAGGCUAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCCGGUGCGUGAGCA ACAUUACAGGCCUGAUCCUGACAAGAGACGGCGGCUCCACCAACUCUACUACCGAGACAUUCCGGCCCGG CGGCGGCGACAUGCGUGAUAACUGGCGCAGCGAACUGUAUAAAUAUAAAGUGGUGAAGAUCGAGCCUC UGGGCGUGGCCCCAACUAGGUGUAAAAGAAGGGUCGUCGGCUCCCACAGCGGCAGCGGCGGCUCCGGCU CUGGCGGCCACGCGGCUGUCGGCAUCGGCGCCGUGAGCCUGGGCUUUCUGGGCGCCGCCGGCUCCACUA UGGGCGCAGCCUCUAUGACCCUGACUGUCCAGGCUAGAAAUCUGCUGUCUGGAAUCGUGCAGCAGCAG UCUAACCUGCUGAGGGCACCUGAGCCACAACAGCACCUGCUGAAGGAUACACAUUGGGGCAUCAAGCAG UUACAAGCCAGGGUGCUGGCCGUGGAACACUACCUGCGCGAUCAGCAAUUACUGGGCAUUUGGGGAUG CUCUGGCAAGCUGAUUUGUUGCACCAAUGUGCCCUGGAACUCCUCUUGGAGCAACAGAAACCUGUCCGA AAUCUGGGAUAACAUGACAUGGCUGCAGUGGGACAAGGAAAUUUCCAAUUAUACCCAGAUCAUCUAUG GACUGCUGGAAGAAAGUCAGAAUCAGCAGGAGAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGC GCCGAAAACCUGUGGGUCACCGUGUAUUAUGGAGUGCCAGUGUGGAAGGACGCCGAGACCACACUGUU UUGUGCCUCUGAUGCCAAGGCCUACGAGACCGAGAAGCACAACGUGUGGGCCACCCACGCCUGCGUGCC CACAGACCCAAAUCCUCAGGAGAUCCACCUGGAGAACGUGACCGAGGAGUUUAACAUGUGGAAGAACAA UAUGGUGGAGCAGAUGCACGAGGAUAUCAUCUCUCUGUGGGAUCAGUCUCUGAAGCCAUGUGUGAAGC UGACCCCACUGUGCGUGACCCUGCAGUGUACAAAUGUGACAAACAACAUCACAGAUGACAUGAGAGGCG AGCUGAAGAACUGUUCCUUCAAUAUGACCACCGAGCUGAGAGACAAGAAGCAGAAGGUGUAUUCUCUG UUUUACCGGCUGGACGUGGUGCAGAUCAACGAGAAUCAGGGCAAUCGGUCUAACAACUCCAAUAAGGA GUAUAGACUGAUCAACUGCAACACCUCUGCCAUCACCCAGGCCUGUCCUAAGGUGUCCUUUGAGCCAAU CCCAAUCCACUAUUGCGCCCCUGCCGGCUUUGCCAUCCUGAAGUGCAAGGACAAGAAGUUUAACGGCAC AGGCCCCUGCCCAUCCGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCUGUGGUGUCCACCCAGCU GCUGCUGAACGGCUCCCUGGCCGAGGAGGAGGUAAUCAUCAGGUCUGAGAACAUCACAAAUAACGCCAA GAACAUCCUGGUGCAGCUGAACACCCCAGUGCAGAUCAACUGUACCCGGCCUAACAAUAAUACCGUGAA GUCUAUCCGGAUCGGCCCAGGCCAGGCCUUCUACUAUACCGGCGAUAUCAUCGGCGAUAUCAGACAGGC CCACUGCAACGUGUCCAAGGCCACAUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGCGGAAGCA CUUUGGCAAUAACACCAUCAUCAGAUUCGCCCAGUCUUCCGGCGGCGACCUGGAGGUGACAACCCACUCC UUCAAUUGCGGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCCUGUUUAAUAGCACCUGGAUCUCUAA CACCUCCGUGCAGGGCUCCAACAGCACAGGCUCUAAUGAUUCCAUCACCCUGCCUUGCCGGAUCAAGCAG AUCAUCAAUAUGUGGCAGAGAAUCGGCCAGGCCAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCCGCUGC GUGUCCAACAUCACAGGCCUGAUCCUGACAAGAGAUGGCGGCUCCACCAACAGCACCACAGAGACCUUCA GACCCGGCGGCGGCGACAUGCGCGACAACUGGAGAUCCGAGCUGUAUAAGUACAAGGUGGUGAAGAUC GAGCCCCUGGGCGUGGCCCCAACCCGGUGUAAGCGCAGAGUGGUGGGCAGCCACAGCGGCAGCGGCGGC AGCGGCUCCGGCGGCCACGCCGCCGUGGGCAUCGGCGCCGUGUCCCUGGGCUUCCUGGGCGCCGCCGGC UCCACCAUGGGCGCCGCCUCCAUGACACUGACAGUGCAGGCCAGAAAUCUGCUGUCCGGCAUCGUGCAG CAGCAGUCCAAUCUGCUGCGGGCCCCUGAGCCACAGCAGCACCUGCUGAAGGAUACCCACUGGGGCAUCA AGCAGCUGCAGGCCCGGGUGCUGGCCGUGGAGCACUACCUGAGGGAUCAGCAGCUGCUGGGCAUCUGG GGCUGUUCCGGCAAGCUGAUCUGCUGUACAAACGUGCCCUGGAACAGCUCCUGGUCCAAUAGGAACCUG UCCGAGAUCUGGGAUAACAUGACCUGGCUGCAGUGGGAUAAGGAGAUCAGCAACUACACACAGAUCAUC UACGGCCUGCUGGAGGAGAGCCAGAAUCAGCAGGAGAAGAACGAGCAGGACCUGCUGGCCCUGGAUUG AUAA (SEQ ID NO: 119) BG505 MD39_TS 2 (amino acid, dna, rna) (longer linker) There were different codon optimizations for each of the repeats Repeat 1: human Repeat 2: human/mouse Repeat 3: mouse MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGAENLWVTVYYGV PVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQ SLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKE YRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEV IIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQL RKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMW QRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKR RVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLK DTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYT QIIYGLLEESQNQQEKNEQDLLALDGGSGSGAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHA CVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELK NCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAI LKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNT VKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGE FFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGS TNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGA AGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCS GKLICCTNVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALD** (SEQ ID NO: 123) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccgtg tggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggatggcggcagcggcagcggcgccgaaaacctgtgggtcaccgtgtactacggagtccccgtgtggaaagatgcagagacaaccctgtt ctgcgcttccgacgctaaagcttacgagacagaaaaacacaacgtgtgggccactcatgcctgcgtgcctacagaccctaacccacaggaaatc cacctggagaatgtgacggaggagtttaacatgtggaagaataacatggtcgagcagatgcatgaagatatcatttccttatgggaccaatccct gaagccttgcgtgaagctgaccccactgtgcgtgacactgcaatgcactaacgtgaccaataacattaccgacgatatgcgcggcgagctgaag aactgctctttcaacatgactaccgagctgagagataagaaacagaaagtgtacagcctgttttatcggttagatgtggtgcagatcaatgaaaa ccagggcaatcggtccaacaattctaacaaggaatatcgcctgatcaattgtaacacctccgccattacccaggcttgccctaaggtgtctttcga gcccatccctatccactattgcgccccagctggatttgctatcctgaagtgtaaggacaaaaagtttaacgggaccggaccatgtcctagcgtgtc cactgtgcagtgcacccatggcatcaagcctgtggtgtccacccaacttctgctgaatggctctctggctgaagaagaagtgatcattaggtccga aaatattactaataacgctaaaaatatcctggtccagctgaacacgcctgtccagatcaattgtacccggccaaataacaacacagtgaagtcta tcagaatcggcccaggccaggccttctactacacaggcgacattatcggcgatattcgccaggcccactgtaatgtgagcaaagctacatggaa tgagacactgggcaaggtagtcaaacagctgagaaaacattttggaaacaacaccatcatccgctttgcacagtctagcggcggcgacctggagg taactacccacagcttcaattgtggcggcgagttcttttactgtaataccagcggcctgtttaatagtacttggatcagcaacacatctgtgcag ggctctaactccactggctctaacgatagcatcacactgccttgtcggatcaagcaaatcatcaacatgtggcaaaggattgggcaggctatgta tgcccctccaatccagggcgtgatccggtgcgtgagcaacattacaggcctgatcctgacaagagacggcggctccaccaactctactaccgag acattccggcccggcggcggcgacatgcgtgataactggcgcagcgaactgtataaatataaagtggtgaagatcgagcctctgggcgtggccc caactaggtgtaaaagaagggtcgtcggctcccacagcggcagcggcggctccggctctggcggccacgcggctgtcggcatcggcgccgtgagc ctgggctttctgggcgccgccggctccactatgggcgcagcctctatgaccctgactgtccaggctagaaatctgctgtctggaatcgtgcagc agcagtctaacctgctgagggcacctgagccacaacagcacctgctgaaggatacacattggggcatcaagcagttacaagccagggtgctggcc gtggaacactacctgcgcgatcagcaattactgggcatttggggatgctctggcaagctgatttgttgcaccaatgtgccctggaactcctctt ggagcaacagaaacctgtccgaaatctgggataacatgacatggctgcagtgggacaaggaaatttccaattatacccagatcatctatggact gctggaagaaagtcagaatcagcaggagaagaatgaacaggatctgctggcactggatggcggcagcggcagcggcgccgaaaacctgtgg gtcaccgtgtattatggagtgccagtgtggaaggacgccgagaccacactgttttgtgcctctgatgccaaggcctacgagaccgagaagcaca acgtgtgggccacccacgcctgcgtgcccacagacccaaatcctcaggagatccacctggagaacgtgaccgaggagtttaacatgtggaaga acaatatggtggagcagatgcacgaggatatcatctctctgtgggatcagtctctgaagccatgtgtgaagctgaccccactgtgcgtgaccctg cagtgtacaaatgtgacaaacaacatcacagatgacatgagaggcgagctgaagaactgttccttcaatatgaccaccgagctgagagacaag aagcagaaggtgtattctctgttttaccggctggacgtggtgcagatcaacgagaatcagggcaatcggtctaacaactccaataaggagtataga ctgatcaactgcaacacctctgccatcacccaggcctgtcctaaggtgtcctttgagccaatcccaatccactattgcgcccctgccggctttgc catcctgaagtgcaaggacaagaagtttaacggcacaggcccctgcccatccgtgagcacagtgcagtgtacccacggcatcaagcctgtggtg tccacccagctgctgctgaacggctccctggccgaggaggaggtaatcatcaggtctgagaacatcacaaataacgccaagaacatcctggtgc agctgaacaccccagtgcagatcaactgtacccggcctaacaataataccgtgaagtctatccggatcggcccaggccaggccttctactatacc ggcgatatcatcggcgatatcagacaggcccactgcaacgtgtccaaggccacatggaacgagacactgggcaaggtggtgaagcagctgcg gaagcactttggcaataacaccatcatcagattcgcccagtcttccggcggcgacctggaggtgacaacccactccttcaattgcggcggcgagtt cttttactgtaatacaagcggcctgtttaatagcacctggatctctaacacctccgtgcagggctccaacagcacaggctctaatgattccatcac cctgccttgccggatcaagcagatcatcaatatgtggcagagaatcggccaggccatgtatgcccctccaatccagggcgtgatccgctgcgtgt ccaacatcacaggcctgatcctgacaagagatggcggctccaccaacagcaccacagagaccttcagacccggcggcggcgacatgcgcgac aactggagatccgagctgtataagtacaaggtggtgaagatcgagcccctgggcgtggccccaacccggtgtaagcgcagagtggtgggcagc cacagcggcagcggcggcagcggctccggcggccacgccgccgtgggcatcggcgccgtgtccctgggcttcctgggcgccgccggctccacc atgggcgccgcctccatgacactgacagtgcaggccagaaatctgctgtccggcatcgtgcagcagcagtccaatctgctgcgggcccctgagc cacagcagcacctgctgaaggatacccactggggcatcaagcagctgcaggcccgggtgctggccgtggagcactacctgagggatcagcagc tgctgggcatctggggctgttccggcaagctgatctgctgtacaaacgtgccctggaacagctcctggtccaataggaacctgtccgagatctgg gataacatgacctggctgcagtgggataaggagatcagcaactacacacagatcatctacggcctgctggaggagagccagaatcagcagga gaagaacgagcaggacctgctggccctggattgataa (SEQ ID NO: 121) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCC ACGCCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCA GCCUCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUG CUGAGAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCA GGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAG CUGAUCUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGA CAAUAUGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGA AGAAUCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGCAGCGGCAGCG GCGCCGAAAACCUGUGGGUCACCGUGUACUACGGAGUCCCCGUGUGGAAAGAUGCAGAGACAACCCUGU UCUGCGCUUCCGACGCUAAAGCUUACGAGACAGAAAAACACAACGUGUGGGCCACUCAUGCCUGCGUGC CUACAGACCCUAACCCACAGGAAAUCCACCUGGAGAAUGUGACGGAGGAGUUUAACAUGUGGAAGAAUA ACAUGGUCGAGCAGAUGCAUGAAGAUAUCAUUUCCUUAUGGGACCAAUCCCUGAAGCCUUGCGUGAAG CUGACCCCACUGUGCGUGACACUGCAAUGCACUAACGUGACCAAUAACAUUACCGACGAUAUGCGCGGC GAGCUGAAGAACUGCUCUUUCAACAUGACUACCGAGCUGAGAGAUAAGAAACAGAAAGUGUACAGCCUG UUUUAUCGGUUAGAUGUGGUGCAGAUCAAUGAAAACCAGGGCAAUCGGUCCAACAAUUCUAACAAGGA AUAUCGCCUGAUCAAUUGUAACACCUCCGCCAUUACCCAGGCUUGCCCUAAGGUGUCUUUCGAGCCCAU CCCUAUCCACUAUUGCGCCCCAGCUGGAUUUGCUAUCCUGAAGUGUAAGGACAAAAAGUUUAACGGGAC CGGACCAUGUCCUAGCGUGUCCACUGUGCAGUGCACCCAUGGCAUCAAGCCUGUGGUGUCCACCCAACU UCUGCUGAAUGGCUCUCUGGCUGAAGAAGAAGUGAUCAUUAGGUCCGAAAAUAUUACUAAUAACGCUA AAAAUAUCCUGGUCCAGCUGAACACGCCUGUCCAGAUCAAUUGUACCCGGCCAAAUAACAACACAGUGAA GUCUAUCAGAAUCGGCCCAGGCCAGGCCUUCUACUACACAGGCGACAUUAUCGGCGAUAUUCGCCAGGC CCACUGUAAUGUGAGCAAAGCUACAUGGAAUGAGACACUGGGCAAGGUAGUCAAACAGCUGAGAAAACA UUUUGGAAACAACACCAUCAUCCGCUUUGCACAGUCUAGCGGCGGCGACCUGGAGGUAACUACCCACAG CUUCAAUUGUGGCGGCGAGUUCUUUUACUGUAAUACCAGCGGCCUGUUUAAUAGUACUUGGAUCAGCA ACACAUCUGUGCAGGGCUCUAACUCCACUGGCUCUAACGAUAGCAUCACACUGCCUUGUCGGAUCAAGC AAAUCAUCAACAUGUGGCAAAGGAUUGGGCAGGCUAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCCGG UGCGUGAGCAACAUUACAGGCCUGAUCCUGACAAGAGACGGCGGCUCCACCAACUCUACUACCGAGACA UUCCGGCCCGGCGGCGGCGACAUGCGUGAUAACUGGCGCAGCGAACUGUAUAAAUAUAAAGUGGUGAA GAUCGAGCCUCUGGGCGUGGCCCCAACUAGGUGUAAAAGAAGGGUCGUCGGCUCCCACAGCGGCAGCGG CGGCUCCGGCUCUGGCGGCCACGCGGCUGUCGGCAUCGGCGCCGUGAGCCUGGGCUUUCUGGGCGCCGC CGGCUCCACUAUGGGCGCAGCCUCUAUGACCCUGACUGUCCAGGCUAGAAAUCUGCUGUCUGGAAUCGU GCAGCAGCAGUCUAACCUGCUGAGGGCACCUGAGCCACAACAGCACCUGCUGAAGGAUACACAUUGGGG CAUCAAGCAGUUACAAGCCAGGGUGCUGGCCGUGGAACACUACCUGCGCGAUCAGCAAUUACUGGGCAU UUGGGGAUGCUCUGGCAAGCUGAUUUGUUGCACCAAUGUGCCCUGGAACUCCUCUUGGAGCAACAGAA ACCUGUCCGAAAUCUGGGAUAACAUGACAUGGCUGCAGUGGGACAAGGAAAUUUCCAAUUAUACCCAGA UCAUCUAUGGACUGCUGGAAGAAAGUCAGAAUCAGCAGGAGAAGAAUGAACAGGAUCUGCUGGCACUG GAUGGCGGCAGCGGCAGCGGCGCCGAAAACCUGUGGGUCACCGUGUAUUAUGGAGUGCCAGUGUGGAA GGACGCCGAGACCACACUGUUUUGUGCCUCUGAUGCCAAGGCCUACGAGACCGAGAAGCACAACGUGUG GGCCACCCACGCCUGCGUGCCCACAGACCCAAAUCCUCAGGAGAUCCACCUGGAGAACGUGACCGAGGAG UUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACGAGGAUAUCAUCUCUCUGUGGGAUCAGUC UCUGAAGCCAUGUGUGAAGCUGACCCCACUGUGCGUGACCCUGCAGUGUACAAAUGUGACAAACAACAU CACAGAUGACAUGAGAGGCGAGCUGAAGAACUGUUCCUUCAAUAUGACCACCGAGCUGAGAGACAAGAA GCAGAAGGUGUAUUCUCUGUUUUACCGGCUGGACGUGGUGCAGAUCAACGAGAAUCAGGGCAAUCGGU CUAACAACUCCAAUAAGGAGUAUAGACUGAUCAACUGCAACACCUCUGCCAUCACCCAGGCCUGUCCUAA GGUGUCCUUUGAGCCAAUCCCAAUCCACUAUUGCGCCCCUGCCGGCUUUGCCAUCCUGAAGUGCAAGGA CAAGAAGUUUAACGGCACAGGCCCCUGCCCAUCCGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCU GUGGUGUCCACCCAGCUGCUGCUGAACGGCUCCCUGGCCGAGGAGGAGGUAAUCAUCAGGUCUGAGAA CAUCACAAAUAACGCCAAGAACAUCCUGGUGCAGCUGAACACCCCAGUGCAGAUCAACUGUACCCGGCCU AACAAUAAUACCGUGAAGUCUAUCCGGAUCGGCCCAGGCCAGGCCUUCUACUAUACCGGCGAUAUCAUC GGCGAUAUCAGACAGGCCCACUGCAACGUGUCCAAGGCCACAUGGAACGAGACACUGGGCAAGGUGGUG AAGCAGCUGCGGAAGCACUUUGGCAAUAACACCAUCAUCAGAUUCGCCCAGUCUUCCGGCGGCGACCUG GAGGUGACAACCCACUCCUUCAAUUGCGGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCCUGUUUAA UAGCACCUGGAUCUCUAACACCUCCGUGCAGGGCUCCAACAGCACAGGCUCUAAUGAUUCCAUCACCCUG CCUUGCCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGAGAAUCGGCCAGGCCAUGUAUGCCCCUCCAAUC CAGGGCGUGAUCCGCUGCGUGUCCAACAUCACAGGCCUGAUCCUGACAAGAGAUGGCGGCUCCACCAAC AGCACCACAGAGACCUUCAGACCCGGCGGCGGCGACAUGCGCGACAACUGGAGAUCCGAGCUGUAUAAG UACAAGGUGGUGAAGAUCGAGCCCCUGGGCGUGGCCCCAACCCGGUGUAAGCGCAGAGUGGUGGGCAG CCACAGCGGCAGCGGCGGCAGCGGCUCCGGCGGCCACGCCGCCGUGGGCAUCGGCGCCGUGUCCCUGGG CUUCCUGGGCGCCGCCGGCUCCACCAUGGGCGCCGCCUCCAUGACACUGACAGUGCAGGCCAGAAAUCUG CUGUCCGGCAUCGUGCAGCAGCAGUCCAAUCUGCUGCGGGCCCCUGAGCCACAGCAGCACCUGCUGAAG GAUACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCCGUGGAGCACUACCUGAGGGAUCAG CAGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGCUGAUCUGCUGUACAAACGUGCCCUGGAACAGCUCC UGGUCCAAUAGGAACCUGUCCGAGAUCUGGGAUAACAUGACCUGGCUGCAGUGGGAUAAGGAGAUCAG CAACUACACACAGAUCAUCUACGGCCUGCUGGAGGAGAGCCAGAAUCAGCAGGAGAAGAACGAGCAGGA CCUGCUGGCCCUGGAUUGAUAA (SEQ ID NO: 122) Membrane bound BG505_MD39_Link14_gp140_PDGFR (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGGSGGSGGSGGSGGSG GSNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKKPR** (SEQ ID NO: 126) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggatggaggaggaagcgggggaagcgggggaagcggaggaagcgggggaagcgggggaagcaacgccgtgggccaggacacccagg aagtgatcgtggtgccccacagcctgcctttcaaggtggtggtcatctccgccatcctggccctggtcgtgctgactattatttccctgatta tcctgattatgctgtggcagaagaagcccagatgataa (SEQ ID NO: 124) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCC ACGCCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCA GCCUCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUG CUGAGAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCA GGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAG CUGAUCUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGA CAAUAUGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGA AGAAUCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAGGAGGAAGCGGGG GAAGCGGGGGAAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAACGCCGUGGGCCAGGACACCCAGGAA GUGAUCGUGGUGCCCCACAGCCUGCCUUUCAAGGUGGUGGUCAUCUCCGCCAUCCUGGCCCUGGUCGU GCUGACUAUUAUUUCCCUGAUUAUCCUGAUUAUGCUGUGGCAGAAGAAGCCCAGAUGAUAA (SEQ ID NO: 125) BG505_MD39_Link14_gp140_Foldon-PDGFR (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGGSGGSGGGYIPEAPRD GQAYVRKDGEWVLLSTFLGGSGGSGGSGGSNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKK PR** (SEQ ID NO: 129) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgccc gtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggatggaggaggaagcgggggaagcggcggcggctacatccctgaggccccaagggacggacaggcctatgtgagaaaggatggcgag tgggtgctgctgtccaccttcctggggggaagcggaggaagcgggggaagcgggggaagcaacgccgtgggccaggacacccaggaagtgat cgtggtgccccacagcctgcctttcaaggtggtggtcatctccgccatcctggccctggtcgtgctgactattatttccctgattatcctgatt atgctgtggcagaagaagcccagatgataa (SEQ ID NO: 127) BG505_MD39_trimer string 1 gp140_PDGFR (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAAS MTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVP WNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVW KDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKP CVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLI NCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRS ENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRK HFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQR IGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVV GSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMGAASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTH WGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSNRNLSEIW/DNMTWLQWDKEISNYTQIIY GLLEESQNQQEKNEQDLLALDGGAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPN PQEIHLENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNM TTELRDKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKK FNGTGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGP GQAFYYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTS GLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTET FRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGIGAVSLGFLGAAGSTMG AASMTLTVQARNLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCT NVPWNSSWSNRNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGGSGGSGGSGGSG GSGGSNAVGQDTQEVIVVPHSLPFKVVVISAILALVVLTIISLIILIMLWQKKPR** (SEQ ID NO: 132) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgccc gtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccg ccatcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggca gcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggctctcacagcggctccggcggctctg gcagcggcggccacgccgcagtgggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccct gacagtgcaggccaggaatctgctgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaagga cacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagc ggcaagctgatctgctgtaccaatgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtg ggataaggagatctccaactacacacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggc actggatggcggcgccgaaaacctgtgggtcaccgtgtactacggagtccccgtgtggaaagatgcagagacaaccctgttctgcgcttccgac gctaaagcttacgagacagaaaaacacaacgtgtgggccactcatgcctgcgtgcctacagaccctaacccacaggaaatccacctggagaat gtgacggaggagtttaacatgtggaagaataacatggtcgagcagatgcatgaagatatcatttccttatgggaccaatccctgaagccttgcgt gaagctgaccccactgtgcgtgacactgcaatgcactaacgtgaccaataacattaccgacgatatgcgcggcgagctgaagaactgctctttc aacatgactaccgagctgagagataagaaacagaaagtgtacagcctgttttatcggttagatgtggtgcagatcaatgaaaaccagggcaat cggtccaacaattctaacaaggaatatcgcctgatcaattgtaacacctccgccattacccaggcttgccctaaggtgtctttcgagcccatccct atccactattgcgccccagctggatttgctatcctgaagtgtaaggacaaaaagtttaacgggaccggaccatgtcctagcgtgtccactgtgca gtgcacccatggcatcaagcctgtggtgtccacccaacttctgctgaatggctctctggctgaagaagaagtgatcattaggtccgaaaatattac taataacgctaaaaatatcctggtccagctgaacacgcctgtccagatcaattgtacccggccaaataacaacacagtgaagtctatcagaatc ggcccaggccaggccttctactacacaggcgacattatcggcgatattcgccaggcccactgtaatgtgagcaaagctacatggaatgagacac tgggcaaggtagtcaaacagctgagaaaacattttggaaacaacaccatcatccgctttgcacagtctagcggcggcgacctggaggtaactac ccacagcttcaattgtggcggcgagttcttttactgtaataccagcggcctgtttaatagtacttggatcagcaacacatctgtgcagggctctaa ctccactggctctaacgatagcatcacactgccttgtcggatcaagcaaatcatcaacatgtggcaaaggattgggcaggctatgtatgcccctcc aatccagggcgtgatccggtgcgtgagcaacattacaggcctgatcctgacaagagacggcggctccaccaactctactaccgagacattccgg cccggcggcggcgacatgcgtgataactggcgcagcgaactgtataaatataaagtggtgaagatcgagcctctgggcgtggccccaactaggt gtaaaagaagggtcgtcggctcccacagcggcagcggcggctccggctctggcggccacgcggctgtcggcatcggcgccgtgagcctgggctt tctgggcgccgccggctccactatgggcgcagcctctatgaccctgactgtccaggctagaaatctgctgtctggaatcgtgcagcagcagtcta acctgctgagggcacctgagccacaacagcacctgctgaaggatacacattggggcatcaagcagttacaagccagggtgctggccgtggaac actacctgcgcgatcagcaattactgggcatttggggatgctctggcaagctgatttgttgcaccaatgtgccctggaactcctcttggagcaac agaaacctgtccgaaatctgggataacatgacatggctgcagtgggacaaggaaatttccaattatacccagatcatctatggactgctggaaga aagtcagaatcagcaggagaagaatgaacaggatctgctggcactggatggcggcgccgaaaacctgtgggtcaccgtgtattatggagtgcc agtgtggaaggacgccgagaccacactgttttgtgcctctgatgccaaggcctacgagaccgagaagcacaacgtgtgggccacccacgcctgc gtgcccacagacccaaatcctcaggagatccacctggagaacgtgaccgaggagtttaacatgtggaagaacaatatggtggagcagatgcac gaggatatcatctctctgtgggatcagtctctgaagccatgtgtgaagctgaccccactgtgcgtgaccctgcagtgtacaaatgtgacaaacaa catcacagatgacatgagaggcgagctgaagaactgttccttcaatatgaccaccgagctgagagacaagaagcagaaggtgtattctctgttt taccggctggacgtggtgcagatcaacgagaatcagggcaatcggtctaacaactccaataaggagtatagactgatcaactgcaacacctctg ccatcacccaggcctgtcctaaggtgtcctttgagccaatcccaatccactattgcgcccctgccggctttgccatcctgaagtgcaaggacaaga agtttaacggcacaggcccctgcccatccgtgagcacagtgcagtgtacccacggcatcaagcctgtggtgtccacccagctgctgctgaacggc tccctggccgaggaggaggtaatcatcaggtctgagaacatcacaaataacgccaagaacatcctggtgcagctgaacaccccagtgcagatc aactgtacccggcctaacaataataccgtgaagtctatccggatcggcccaggccaggccttctactataccggcgatatcatcggcgatatcag acaggcccactgcaacgtgtccaaggccacatggaacgagacactgggcaaggtggtgaagcagctgcggaagcactttggcaataacacca tcatcagattcgcccagtcttccggcggcgacctggaggtgacaacccactccttcaattgcggcggcgagttcttttactgtaatacaagcggcc tgtttaatagcacctggatctctaacacctccgtgcagggctccaacagcacaggctctaatgattccatcaccctgccttgccggatcaagcaga tcatcaatatgtggcagagaatcggccaggccatgtatgcccctccaatccagggcgtgatccgctgcgtgtccaacatcacaggcctgatcctg acaagagatggcggctccaccaacagcaccacagagaccttcagacccggcggcggcgacatgcgcgacaactggagatccgagctgtataa gtacaaggtggtgaagatcgagcccctgggcgtggccccaacccggtgtaagcgcagagtggtgggcagccacagcggcagcggcggcagcg gctccggcggccacgccgccgtgggcatcggcgccgtgtccctgggcttcctgggcgccgccggctccaccatgggcgccgcctccatgacactg acagtgcaggccagaaatctgctgtccggcatcgtgcagcagcagtccaatctgctgcgggcccctgagccacagcagcacctgctgaaggata cccactggggcatcaagcagctgcaggcccgggtgctggccgtggagcactacctgagggatcagcagctgctgggcatctggggctgttccgg caagctgatctgctgtacaaacgtgccctggaacagctcctggtccaataggaacctgtccgagatctgggataacatgacctggctgcagtggg ataaggagatcagcaactacacacagatcatctacggcctgctggaggagagccagaatcagcaggagaagaacgagcaggacctgctggcc ctggatggaggaggaagcgggggaagcgggggaagcggaggaagcgggggaagcgggggaagcaacgccgtgggccaggacacccagga agtgatcgtggtgccccacagcctgcctttcaaggtggtggtcatctccgccatcctggccctggtcgtgctgactattatttccctgattat cctgattatgctgtggcagaagaagcccagatgataa (SEQ ID NO: 130) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCC ACGCCGCAGUGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCA GCCUCUAUGACCCUGACAGUGCAGGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUG CUGAGAGCCCCAGAGCCCCAGCAGCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCA GGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAG CUGAUCUGCUGUACCAAUGUGCCCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGA CAAUAUGACCUGGCUGCAGUGGGAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGA AGAAUCUCAGAAUCAGCAGGAAAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGCGCCGAAAACCU GUGGGUCACCGUGUACUACGGAGUCCCCGUGUGGAAAGAUGCAGAGACAACCCUGUUCUGCGCUUCCG ACGCUAAAGCUUACGAGACAGAAAAACACAACGUGUGGGCCACUCAUGCCUGCGUGCCUACAGACCCUAA CCCACAGGAAAUCCACCUGGAGAAUGUGACGGAGGAGUUUAACAUGUGGAAGAAUAACAUGGUCGAGC AGAUGCAUGAAGAUAUCAUUUCCUUAUGGGACCAAUCCCUGAAGCCUUGCGUGAAGCUGACCCCACUGU GCGUGACACUGCAAUGCACUAACGUGACCAAUAACAUUACCGACGAUAUGCGCGGCGAGCUGAAGAACU GCUCUUUCAACAUGACUACCGAGCUGAGAGAUAAGAAACAGAAAGUGUACAGCCUGUUUUAUCGGUUA GAUGUGGUGCAGAUCAAUGAAAACCAGGGCAAUCGGUCCAACAAUUCUAACAAGGAAUAUCGCCUGAUC AAUUGUAACACCUCCGCCAUUACCCAGGCUUGCCCUAAGGUGUCUUUCGAGCCCAUCCCUAUCCACUAU UGCGCCCCAGCUGGAUUUGCUAUCCUGAAGUGUAAGGACAAAAAGUUUAACGGGACCGGACCAUGUCC UAGCGUGUCCACUGUGCAGUGCACCCAUGGCAUCAAGCCUGUGGUGUCCACCCAACUUCUGCUGAAUGG CUCUCUGGCUGAAGAAGAAGUGAUCAUUAGGUCCGAAAAUAUUACUAAUAACGCUAAAAAUAUCCUGG UCCAGCUGAACACGCCUGUCCAGAUCAAUUGUACCCGGCCAAAUAACAACACAGUGAAGUCUAUCAGAA UCGGCCCAGGCCAGGCCUUCUACUACACAGGCGACAUUAUCGGCGAUAUUCGCCAGGCCCACUGUAAUG UGAGCAAAGCUACAUGGAAUGAGACACUGGGCAAGGUAGUCAAACAGCUGAGAAAACAUUUUGGAAAC AACACCAUCAUCCGCUUUGCACAGUCUAGCGGCGGCGACCUGGAGGUAACUACCCACAGCUUCAAUUGU GGCGGCGAGUUCUUUUACUGUAAUACCAGCGGCCUGUUUAAUAGUACUUGGAUCAGCAACACAUCUGU GCAGGGCUCUAACUCCACUGGCUCUAACGAUAGCAUCACACUGCCUUGUCGGAUCAAGCAAAUCAUCAA CAUGUGGCAAAGGAUUGGGCAGGCUAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCCGGUGCGUGAGCA ACAUUACAGGCCUGAUCCUGACAAGAGACGGCGGCUCCACCAACUCUACUACCGAGACAUUCCGGCCCGG CGGCGGCGACAUGCGUGAUAACUGGCGCAGCGAACUGUAUAAAUAUAAAGUGGUGAAGAUCGAGCCUC UGGGCGUGGCCCCAACUAGGUGUAAAAGAAGGGUCGUCGGCUCCCACAGCGGCAGCGGCGGCUCCGGCU CUGGCGGCCACGCGGCUGUCGGCAUCGGCGCCGUGAGCCUGGGCUUUCUGGGCGCCGCCGGCUCCACUA UGGGCGCAGCCUCUAUGACCCUGACUGUCCAGGCUAGAAAUCUGCUGUCUGGAAUCGUGCAGCAGCAG UCUAACCUGCUGAGGGCACCUGAGCCACAACAGCACCUGCUGAAGGAUACACAUUGGGGCAUCAAGCAG UUACAAGCCAGGGUGCUGGCCGUGGAACACUACCUGCGCGAUCAGCAAUUACUGGGCAUUUGGGGAUG CUCUGGCAAGCUGAUUUGUUGCACCAAUGUGCCCUGGAACUCCUCUUGGAGCAACAGAAACCUGUCCGA AAUCUGGGAUAACAUGACAUGGCUGCAGUGGGACAAGGAAAUUUCCAAUUAUACCCAGAUCAUCUAUG GACUGCUGGAAGAAAGUCAGAAUCAGCAGGAGAAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGC GCCGAAAACCUGUGGGUCACCGUGUAUUAUGGAGUGCCAGUGUGGAAGGACGCCGAGACCACACUGUU UUGUGCCUCUGAUGCCAAGGCCUACGAGACCGAGAAGCACAACGUGUGGGCCACCCACGCCUGCGUGCC CACAGACCCAAAUCCUCAGGAGAUCCACCUGGAGAACGUGACCGAGGAGUUUAACAUGUGGAAGAACAA UAUGGUGGAGCAGAUGCACGAGGAUAUCAUCUCUCUGUGGGAUCAGUCUCUGAAGCCAUGUGUGAAGC UGACCCCACUGUGCGUGACCCUGCAGUGUACAAAUGUGACAAACAACAUCACAGAUGACAUGAGAGGCG AGCUGAAGAACUGUUCCUUCAAUAUGACCACCGAGCUGAGAGACAAGAAGCAGAAGGUGUAUUCUCUG UUUUACCGGCUGGACGUGGUGCAGAUCAACGAGAAUCAGGGCAAUCGGUCUAACAACUCCAAUAAGGA GUAUAGACUGAUCAACUGCAACACCUCUGCCAUCACCCAGGCCUGUCCUAAGGUGUCCUUUGAGCCAAU CCCAAUCCACUAUUGCGCCCCUGCCGGCUUUGCCAUCCUGAAGUGCAAGGACAAGAAGUUUAACGGCAC AGGCCCCUGCCCAUCCGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCUGUGGUGUCCACCCAGCU GCUGCUGAACGGCUCCCUGGCCGAGGAGGAGGUAAUCAUCAGGUCUGAGAACAUCACAAAUAACGCCAA GAACAUCCUGGUGCAGCUGAACACCCCAGUGCAGAUCAACUGUACCCGGCCUAACAAUAAUACCGUGAA GUCUAUCCGGAUCGGCCCAGGCCAGGCCUUCUACUAUACCGGCGAUAUCAUCGGCGAUAUCAGACAGGC CCACUGCAACGUGUCCAAGGCCACAUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGCGGAAGCA CUUUGGCAAUAACACCAUCAUCAGAUUCGCCCAGUCUUCCGGCGGCGACCUGGAGGUGACAACCCACUCC UUCAAUUGCGGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCCUGUUUAAUAGCACCUGGAUCUCUAA CACCUCCGUGCAGGGCUCCAACAGCACAGGCUCUAAUGAUUCCAUCACCCUGCCUUGCCGGAUCAAGCAG AUCAUCAAUAUGUGGCAGAGAAUCGGCCAGGCCAUGUAUGCCCCUCCAAUCCAGGGCGUGAUCCGCUGC GUGUCCAACAUCACAGGCCUGAUCCUGACAAGAGAUGGCGGCUCCACCAACAGCACCACAGAGACCUUCA GACCCGGCGGCGGCGACAUGCGCGACAACUGGAGAUCCGAGCUGUAUAAGUACAAGGUGGUGAAGAUC GAGCCCCUGGGCGUGGCCCCAACCCGGUGUAAGCGCAGAGUGGUGGGCAGCCACAGCGGCAGCGGCGGC AGCGGCUCCGGCGGCCACGCCGCCGUGGGCAUCGGCGCCGUGUCCCUGGGCUUCCUGGGCGCCGCCGGC UCCACCAUGGGCGCCGCCUCCAUGACACUGACAGUGCAGGCCAGAAAUCUGCUGUCCGGCAUCGUGCAG CAGCAGUCCAAUCUGCUGCGGGCCCCUGAGCCACAGCAGCACCUGCUGAAGGAUACCCACUGGGGCAUCA AGCAGCUGCAGGCCCGGGUGCUGGCCGUGGAGCACUACCUGAGGGAUCAGCAGCUGCUGGGCAUCUGG GGCUGUUCCGGCAAGCUGAUCUGCUGUACAAACGUGCCCUGGAACAGCUCCUGGUCCAAUAGGAACCUG UCCGAGAUCUGGGAUAACAUGACCUGGCUGCAGUGGGAUAAGGAGAUCAGCAACUACACACAGAUCAUC UACGGCCUGCUGGAGGAGAGCCAGAAUCAGCAGGAGAAGAACGAGCAGGACCUGCUGGCCCUGGAUGG AGGAGGAAGCGGGGGAAGCGGGGGAAGCGGAGGAAGCGGGGGAAGCGGGGGAAGCAACGCCGUGGGCC AGGACACCCAGGAAGUGAUCGUGGUGCCCCACAGCCUGCCUUUCAAGGUGGUGGUCAUCUCCGCCAUCC UGGCCCUGGUCGUGCUGACUAUUAUUUCCCUGAUUAUCCUGAUUAUGCUGUGGCAGAAGAAGCCCAGA UGAUAA (SEQ ID NO: 131) Nanoparticles BG505_MD39_3BVE (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGSGGLSKDIIKLLNEQVNKEMQSSNLY MSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESIN NIVDHAIKSKDHATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKS** (SEQ ID NO: 156) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgccc gtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgc catcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggaagcggcgggctga gtaaggacattatcaagctgctgaacgaacaggtgaacaaagagatgcagtctagcaacctgtacatgtccatgagctcctggtgctataccca ctctctggacggagcaggcctgttcctgtttgatcacgccgccgaggagtacgagcacgccaagaagctgatcatcttcctgaatgagaacaatg tgcccgtgcagctgacctctatcagcgcccctgagcacaagttcgagggcctgacacagatctttcagaaggcctacgagcacgagcagcacat ctccgagtctatcaacaatatcgtggaccacgccatcaagtccaaggatcacgccacattcaactttctgcagtggtacgtggccgagcagcac gaggaggaggtgctgtttaaggacatcctggataagatcgagctgatcggcaatgagaaccacgggctgtacctggcagatcagtatgtcaagg gcatcgctaagtcaaggaaaagctgataa (SEQ ID NO: 154) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAAGCGGCGGGCUGAGUAAGGACAUUAUCAAGCUGCU GAACGAACAGGUGAACAAAGAGAUGCAGUCUAGCAACCUGUACAUGUCCAUGAGCUCCUGGUGCUAUAC CCACUCUCUGGACGGAGCAGGCCUGUUCCUGUUUGAUCACGCCGCCGAGGAGUACGAGCACGCCAAGAA GCUGAUCAUCUUCCUGAAUGAGAACAAUGUGCCCGUGCAGCUGACCUCUAUCAGCGCCCCUGAGCACAA GUUCGAGGGCCUGACACAGAUCUUUCAGAAGGCCUACGAGCACGAGCAGCACAUCUCCGAGUCUAUCAA CAAUAUCGUGGACCACGCCAUCAAGUCCAAGGAUCACGCCACAUUCAACUUUCUGCAGUGGUACGUGGC CGAGCAGCACGAGGAGGAGGUGCUGUUUAAGGACAUCCUGGAUAAGAUCGAGCUGAUCGGCAAUGAGA ACCACGGGCUGUACCUGGCAGAUCAGUAUGUCAAGGGCAUCGCUAAGUCAAGGAAAAGCUGAUAA (SEQ ID NO: 155) BG505_MD39_I3_1 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGGSGGMKMEELFKKHKIVAVL RANSVEEAKKKALAVFLGGVHLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQCRKAVESGAEFIVSPHLDEEI SQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVCEWFK AGVLAVGVGSALVKGTPVEVAEKAKAFVEKIRGCTE** (SEQ ID NO: 159) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgcc atcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatgg cagcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggcggcagcggcagcg gcgggagcggaggaatgaagatggaagaactgttcaagaagcacaagatcgtggccgtgctgagggccaactccgtggaggaggccaagaagaa ggccctggccgtgttcctgggcggcgtgcacctgatcgagatcacctttacagtgcccgacgccgataccgtgatcaaggagctgtctttcct gaaggagatgggagcaatcatcggagcaggaaccgtgacaagcgtggagcagtgcagaaaggccgtggagagcggcgccgagtttatcgtgt cccctcacctggacgaggagatctctcagttctgtaaggagaagggcgtgttttacatgccaggcgtgatgacccccacagagctggtgaaggc catgaagctgggccacacaatcctgaagctgttccctggcgaggtggtgggcccacagtttgtgaaggccatgaagggccccttccctaatgtga agtttgtgcccaccggcggcgtgaacctggataacgtgtgcgagtggttcaaggcaggcgtgctggcagtgggcgtgggcagcgccctggtgaa gggcacacccgtggaagtcgctgagaaggcaaaggcattcgtggaaaagattagggggtgtactgagtgataa (SEQ ID NO: 157) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGCAGCGGCAGCGGCGGGAGCGGAGGAAUGAAGAU GGAAGAACUGUUCAAGAAGCACAAGAUCGUGGCCGUGCUGAGGGCCAACUCCGUGGAGGAGGCCAAGA AGAAGGCCCUGGCCGUGUUCCUGGGCGGCGUGCACCUGAUCGAGAUCACCUUUACAGUGCCCGACGCCG AUACCGUGAUCAAGGAGCUGUCUUUCCUGAAGGAGAUGGGAGCAAUCAUCGGAGCAGGAACCGUGACA AGCGUGGAGCAGUGCAGAAAGGCCGUGGAGAGCGGCGCCGAGUUUAUCGUGUCCCCUCACCUGGACGA GGAGAUCUCUCAGUUCUGUAAGGAGAAGGGCGUGUUUUACAUGCCAGGCGUGAUGACCCCCACAGAGC UGGUGAAGGCCAUGAAGCUGGGCCACACAAUCCUGAAGCUGUUCCCUGGCGAGGUGGUGGGCCCACAG UUUGUGAAGGCCAUGAAGGGCCCCUUCCCUAAUGUGAAGUUUGUGCCCACCGGCGGCGUGAACCUGGA UAACGUGUGCGAGUGGUUCAAGGCAGGCGUGCUGGCAGUGGGCGUGGGCAGCGCCCUGGUGAAGGGC ACACCCGUGGAAGUCGCUGAGAAGGCAAAGGCAUUCGUGGAAAAGAUUAGGGGGUGUACUGAGUGAUA A (SEQ ID NO: 158) BG505_MD39_I3_2 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSDMRKDAERRFDKFVEAAKNKFDK FKAALRKGDIKEERRKDMKKLARKEAEQARRAVRNRLSELLSKINDMPITNDQKKLMSNDVLKFAAEAEKKIEALAA DAEGGSGSMKMEELFKKHKIVAVLRANSVEEAKKKALAVFLGGVHLIEITFTVPDADTVIKELSFLKEMGAIIGAGTV TSVEQCRKAVESGAEFIVSPHLDEEISQFCKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKG PFPNVKFVPTGGVNLDNVCEWFKAGVLAVGVGSALVKGTPVEVAEKAKAFVEKIRGCTE** (SEQ ID NO: 162) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgc catcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggagggagcgatatga gaaaggacgccgagagacggtttgataagttcgtggaggctgctaagaataagtttgacaagtttaaggctgccctgcggaagggcgacatca aggaggagaggagaaaggatatgaagaagctggcaaggaaggaggcagagcaggcaaggagggccgtgaggaacagactgagcgagctg ctgtccaagatcaacgacatgcccatcaccaatgatcagaagaagctgatgtctaatgacgtgctgaagttcgccgcagaagccgaaaagaag attgaagccctggcagcagacgccgaaggaggaagcgggagcatgaagatggaagaactgttcaagaagcacaagatcgtggccgtgctga gggccaactccgtggaggaggccaagaagaaggccctggccgtgttcctgggcggcgtgcacctgatcgagatcacctttacagtgcccgacgc cgataccgtgatcaaggagctgtctttcctgaaggagatgggagcaatcatcggagcaggaaccgtgacaagcgtggagcagtgcagaaagg ccgtggagagcggcgccgagtttatcgtgtcccctcacctggacgaggagatctctcagttctgtaaggagaagggcgtgttttacatgccaggc gtgatgacccccacagagctggtgaaggccatgaagctgggccacacaatcctgaagctgttccctggcgaggtggtgggcccacagtttgtga aggccatgaagggccccttccctaatgtgaagtttgtgcccaccggcggcgtgaacctggataacgtgtgcgagtggttcaaggcaggcgtgctg gcagtgggcgtgggcagcgccctggtgaagggcacacccgtggaagtcgctgagaaggcaaaggcattcgtggaaaagattagggggtgtac tgagtgataa (SEQ ID NO: 160) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAGGGAGCGAUAUGAGAAAGGACGCCGAGAGACGGUU UGAUAAGUUCGUGGAGGCUGCUAAGAAUAAGUUUGACAAGUUUAAGGCUGCCCUGCGGAAGGGCGACA UCAAGGAGGAGAGGAGAAAGGAUAUGAAGAAGCUGGCAAGGAAGGAGGCAGAGCAGGCAAGGAGGGCC GUGAGGAACAGACUGAGCGAGCUGCUGUCCAAGAUCAACGACAUGCCCAUCACCAAUGAUCAGAAGAAG CUGAUGUCUAAUGACGUGCUGAAGUUCGCCGCAGAAGCCGAAAAGAAGAUUGAAGCCCUGGCAGCAGAC GCCGAAGGAGGAAGCGGGAGCAUGAAGAUGGAAGAACUGUUCAAGAAGCACAAGAUCGUGGCCGUGCU GAGGGCCAACUCCGUGGAGGAGGCCAAGAAGAAGGCCCUGGCCGUGUUCCUGGGCGGCGUGCACCUGA UCGAGAUCACCUUUACAGUGCCCGACGCCGAUACCGUGAUCAAGGAGCUGUCUUUCCUGAAGGAGAUG GGAGCAAUCAUCGGAGCAGGAACCGUGACAAGCGUGGAGCAGUGCAGAAAGGCCGUGGAGAGCGGCGCC GAGUUUAUCGUGUCCCCUCACCUGGACGAGGAGAUCUCUCAGUUCUGUAAGGAGAAGGGCGUGUUUUA CAUGCCAGGCGUGAUGACCCCCACAGAGCUGGUGAAGGCCAUGAAGCUGGGCCACACAAUCCUGAAGCU GUUCCCUGGCGAGGUGGUGGGCCCACAGUUUGUGAAGGCCAUGAAGGGCCCCUUCCCUAAUGUGAAGU UUGUGCCCACCGGCGGCGUGAACCUGGAUAACGUGUGCGAGUGGUUCAAGGCAGGCGUGCUGGCAGUG GGCGUGGGCAGCGCCCUGGUGAAGGGCACACCCGUGGAAGUCGCUGAGAAGGCAAAGGCAUUCGUGGA AAAGAUUAGGGGGUGUACUGAGUGAUAA (SEQ ID NO: 161) BG505_MD39_LS_3CBPIX_1 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSSGKSLVDTVYALKDEVQELRQDNK

atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgcc atcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatgg cagcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatgggggctctagcggga aaagtctggtggataccgtctatgctctgaaagatgaggtgcaggaactgaggcaggacaacaaaaagatgaagaagagcctggaggagga gcagagggccagaaaggacctggaaaaactggtgcggaaagtgctgaaaaacatgaatgacggagggagtagcgggatgcagatctacgaa ggaaaactgaccgctgagggactgaggttcggaattgtcgcaagccgcgcgaatcacgcactggtggataggctggtggaaggcgctatcgac gcaattgtccggcacggcgggagagaggaagacatcacactggtgagagtctgcggcagctgggagattcccgtggcagctggagaactggct cgaaaggaggacatcgatgccgtgatcgctattggggtcctgtgccgaggagcaactcccagcttcgactacatcgcctcagaagtgagcaagg ggctggctgatctgtccctggagctgaggaaacctatcacttttggcgtgattactgccgacaccctggaacaggcaatcgaggcggccggcacc tgccatggaaacaaaggctgggaagcagccctgtgcgctattgagatggcaaatctgttcaaatctctgcgatgataa (SEQ ID NO: 163) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGGGGCUCUAGCGGGAAAAGUCUGGUGGAUACCGUCUA UGCUCUGAAAGAUGAGGUGCAGGAACUGAGGCAGGACAACAAAAAGAUGAAGAAGAGCCUGGAGGAGG AGCAGAGGGCCAGAAAGGACCUGGAAAAACUGGUGCGGAAAGUGCUGAAAAACAUGAAUGACGGAGGG AGUAGCGGGAUGCAGAUCUACGAAGGAAAACUGACCGCUGAGGGACUGAGGUUCGGAAUUGUCGCAAG CCGCGCGAAUCACGCACUGGUGGAUAGGCUGGUGGAAGGCGCUAUCGACGCAAUUGUCCGGCACGGCG GGAGAGAGGAAGACAUCACACUGGUGAGAGUCUGCGGCAGCUGGGAGAUUCCCGUGGCAGCUGGAGAA CUGGCUCGAAAGGAGGACAUCGAUGCCGUGAUCGCUAUUGGGGUCCUGUGCCGAGGAGCAACUCCCAG CUUCGACUACAUCGCCUCAGAAGUGAGCAAGGGGCUGGCUGAUCUGUCCCUGGAGCUGAGGAAACCUA UCACUUUUGGCGUGAUUACUGCCGACACCCUGGAACAGGCAAUCGAGGCGGCCGGCACCUGCCAUGGAA ACAAAGGCUGGGAAGCAGCCCUGUGCGCUAUUGAGAUGGCAAAUCUGUUCAAAUCUCUGCGAUGAUAA (SEQ ID NO: 164) BG505_MD39_LS_3CBPIX_2 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSSGADPKKVLDKAKDQAENRVREL KQKLEELYKEARKLDLTQEMRRKLELRYIAAMLMAIGDIYNAIRQAKQEADKLKKAGLVNSQQLDELKRRLEELKEE ASRKARDYGREFQLKLEYGGGSGSGSGMQIYEGKLTAEGLRFGIVASRANHALVDRLVEGAIDAIVRHGGREEDITL VRVCGSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGT CHGNKGWEAALCAIEMANLFKSLR** (SEQ ID NO: 168) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgccc gtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgc catcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatgggggctctagcgggg cagacccaaagaaagtgctggataaggcaaaggatcaggcagagaatagagtgagagaactgaaacagaaactggaggaactgtataagg aggcccggaagctggacctgacccaggagatgaggagaaagctggagctgcgctacatcgccgccatgctgatggccatcggcgacatctata acgccatcaggcaggccaagcaggaggccgataagctgaagaaggccggcctggtgaatagccagcagctggacgagctgaagcggcgcct ggaggagctgaaggaggaggcctccaggaaggccagagattatgggcgggaatttcagctgaaactggagtatggcggcggaagcggaagc gggagcgggatgcagatctacgaaggaaaactgaccgctgagggactgaggttcggaattgtcgcaagccgcgcgaatcacgcactggtggat aggctggtggaaggcgctatcgacgcaattgtccggcacggcgggagagaggaagacatcacactggtgagagtctgcggcagctgggagatt cccgtggcagctggagaactggctcgaaaggaggacatcgatgccgtgatcgctattggggtcctgtgccgaggagcaactcccagcttcgact acatcgcctcagaagtgagcaaggggctggctgatctgtccctggagctgaggaaacctatcacttttggcgtgattactgccgacaccctggaa caggcaatcgaggcggccggcacctgccatggaaacaaaggctgggaagcagccctgtgcgctattgagatggcaaatctgttcaaatctctgc gatgataa (SEQ ID NO: 166) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGGGGCUCUAGCGGGGCAGACCCAAAGAAAGUGCUGGA UAAGGCAAAGGAUCAGGCAGAGAAUAGAGUGAGAGAACUGAAACAGAAACUGGAGGAACUGUAUAAGG AGGCCCGGAAGCUGGACCUGACCCAGGAGAUGAGGAGAAAGCUGGAGCUGCGCUACAUCGCCGCCAUGC UGAUGGCCAUCGGCGACAUCUAUAACGCCAUCAGGCAGGCCAAGCAGGAGGCCGAUAAGCUGAAGAAGG CCGGCCUGGUGAAUAGCCAGCAGCUGGACGAGCUGAAGCGGCGCCUGGAGGAGCUGAAGGAGGAGGCC UCCAGGAAGGCCAGAGAUUAUGGGCGGGAAUUUCAGCUGAAACUGGAGUAUGGCGGCGGAAGCGGAAG CGGGAGCGGGAUGCAGAUCUACGAAGGAAAACUGACCGCUGAGGGACUGAGGUUCGGAAUUGUCGCAA GCCGCGCGAAUCACGCACUGGUGGAUAGGCUGGUGGAAGGCGCUAUCGACGCAAUUGUCCGGCACGGC GGGAGAGAGGAAGACAUCACACUGGUGAGAGUCUGCGGCAGCUGGGAGAUUCCCGUGGCAGCUGGAGA ACUGGCUCGAAAGGAGGACAUCGAUGCCGUGAUCGCUAUUGGGGUCCUGUGCCGAGGAGCAACUCCCA GCUUCGACUACAUCGCCUCAGAAGUGAGCAAGGGGCUGGCUGAUCUGUCCCUGGAGCUGAGGAAACCU AUCACUUUUGGCGUGAUUACUGCCGACACCCUGGAACAGGCAAUCGAGGCGGCCGGCACCUGCCAUGGA AACAAAGGCUGGGAAGCAGCCCUGUGCGCUAUUGAGAUGGCAAAUCUGUUCAAAUCUCUGCGAUGAUA A (SEQ ID NO: 167) BG505_MD39_QB_1 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSSGGTDVGAIAGKANEAGQGAYDA QVKNDEQDVELADHEARIKQLRIDVDDHESRITANTKAITALNVRVTTAEGEIASLQTNVSALDGRVTTAENNISAL QADYVSGGSSGSGAKLETVTLGNIGKDGKQTLVLNPRGVNPTNGVASLSQAGAVPALEKRVTVSVSQPSRNRKNY KVQVKIQNPTACTANGSCDPSVTRQAYADVTFSFTQYSTDEERAFVRTELAALLASPLLIDAIDQLNPAY** (SEQ ID NO: 171) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgc catcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggaggctcttcaggcg gcacagacgtgggggcaatcgctggaaaggctaacgaggctggacagggggcttatgatgctcaggtcaaaaacgacgagcaggatgtggag ctggccgaccacgaggccaggatcaagcagctgagaatcgatgtggacgatcacgagtctcggatcaccgccaacacaaaggccatcacagc cctgaatgtgcgcgtgaccacagcagagggagagatcgcatccctgcagaccaacgtgagcgccctggacggaagggtgaccacagcagaga acaatatctccgccctgcaggcagattacgtgagcggcggcagctccggctccggagcaaagctggagacagtgacactgggcaacatcggca aggacggcaagcagacactggtgctgaatcccaggggcgtgaaccctaccaatggagtggcatctctgagccaggcaggagcagtgcctgccc tggagaagagagtgaccgtgtccgtgtctcagcccagcaggaacagaaagaattataaggtgcaggtgaagatccagaacccaaccgcctgc acagccaatggcagctgtgacccatccgtgacaaggcaggcatacgcagatgtgaccttctcttttacacagtatagcaccgatgaggagaggg ccttcgtgcgcaccgagctggccgccctgctggcatcccctctgctgattgacgctattgaccagctgaaccctgcttactgataa (SEQ ID NO: 169) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAGGCUCUUCAGGCGGCACAGACGUGGGGGCAAUCGC UGGAAAGGCUAACGAGGCUGGACAGGGGGCUUAUGAUGCUCAGGUCAAAAACGACGAGCAGGAUGUGG AGCUGGCCGACCACGAGGCCAGGAUCAAGCAGCUGAGAAUCGAUGUGGACGAUCACGAGUCUCGGAUCA CCGCCAACACAAAGGCCAUCACAGCCCUGAAUGUGCGCGUGACCACAGCAGAGGGAGAGAUCGCAUCCCU GCAGACCAACGUGAGCGCCCUGGACGGAAGGGUGACCACAGCAGAGAACAAUAUCUCCGCCCUGCAGGC AGAUUACGUGAGCGGCGGCAGCUCCGGCUCCGGAGCAAAGCUGGAGACAGUGACACUGGGCAACAUCGG CAAGGACGGCAAGCAGACACUGGUGCUGAAUCCCAGGGGCGUGAACCCUACCAAUGGAGUGGCAUCUCU GAGCCAGGCAGGAGCAGUGCCUGCCCUGGAGAAGAGAGUGACCGUGUCCGUGUCUCAGCCCAGCAGGAA CAGAAAGAAUUAUAAGGUGCAGGUGAAGAUCCAGAACCCAACCGCCUGCACAGCCAAUGGCAGCUGUGA CCCAUCCGUGACAAGGCAGGCAUACGCAGAUGUGACCUUCUCUUUUACACAGUAUAGCACCGAUGAGGA GAGGGCCUUCGUGCGCACCGAGCUGGCCGCCCUGCUGGCAUCCCCUCUGCUGAUUGACGCUAUUGACCA GCUGAACCCUGCUUACUGAUAA (SEQ ID NO: 170) BG505_MD39_QB_2 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGGSSGPHMIAPGHRDEFDPKL PTGEKEEVPGKPGIKNPETGDVVRPPVDSVTKYGPVKGDSIVEKEEIPFEKERKFNPDLAPGTEKVTREGQKGEKTIT TPTLKNPLTGEIISKGESKEEITKDPINELTEWGPETGGSGSGGSSAKLETVTLGNIGKDGKQTLVLNPRGVNPTNGV ASLSQAGAVPALEKRVTVSVSQPSRNRKNYKVQVKIQNPTACTANGSCDPSVTRQAYADVTFSFTQYSTDEERAFV RTELAALLASPLLIDAIDQLNPAY** (SEQ ID NO: 174) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgccc gtgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcg tgcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgc catcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggaggctctggaagcg ggggaagtagcggacctcacatgattgctccaggacatcgggacgagtttgaccctaagctgccaacaggcgagaaagaagaggtgccaggc aagcccggcatcaagaaccctgagacaggcgacgtggtgaggccccctgtggattctgtgacaaagtacggcccagtgaagggcgacagcatc gtggagaaggaggagatccccttcgagaaggagaggaagtttaaccctgatctggccccaggcaccgagaaggtgacaagagagggccaga agggcgagaagaccatcaccacacccacactgaagaatcctctgaccggcgagatcatcagcaagggcgagtccaaggaggagatcacaaa ggaccccatcaacgaactgaccgaatggggaccagagacaggaggaagcggcagcggcggaagcagcgcaaagctggagacagtgacact gggcaacatcggcaaggacggcaagcagacactggtgctgaatcccaggggcgtgaaccctaccaatggagtggcatctctgagccaggcag gagcagtgcctgccctggagaagagagtgaccgtgtccgtgtctcagcccagcaggaacagaaagaattataaggtgcaggtgaagatccaga acccaaccgcctgcacagccaatggcagctgtgacccatccgtgacaaggcaggcatacgcagatgtgaccttctcttttacacagtatagcacc gatgaggagagggccttcgtgcgcaccgagctggccgccctgctggcatcccctctgctgattgacgctattgaccagctgaaccctgcttac tgataa (SEQ ID NO: 172) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAGGCUCUGGAAGCGGGGGAAGUAGCGGACCUCACAU GAUUGCUCCAGGACAUCGGGACGAGUUUGACCCUAAGCUGCCAACAGGCGAGAAAGAAGAGGUGCCAGG CAAGCCCGGCAUCAAGAACCCUGAGACAGGCGACGUGGUGAGGCCCCCUGUGGAUUCUGUGACAAAGUA CGGCCCAGUGAAGGGCGACAGCAUCGUGGAGAAGGAGGAGAUCCCCUUCGAGAAGGAGAGGAAGUUUA ACCCUGAUCUGGCCCCAGGCACCGAGAAGGUGACAAGAGAGGGCCAGAAGGGCGAGAAGACCAUCACCAC ACCCACACUGAAGAAUCCUCUGACCGGCGAGAUCAUCAGCAAGGGCGAGUCCAAGGAGGAGAUCACAAA GGACCCCAUCAACGAACUGACCGAAUGGGGACCAGAGACAGGAGGAAGCGGCAGCGGCGGAAGCAGCGC AAAGCUGGAGACAGUGACACUGGGCAACAUCGGCAAGGACGGCAAGCAGACACUGGUGCUGAAUCCCAG GGGCGUGAACCCUACCAAUGGAGUGGCAUCUCUGAGCCAGGCAGGAGCAGUGCCUGCCCUGGAGAAGA GAGUGACCGUGUCCGUGUCUCAGCCCAGCAGGAACAGAAAGAAUUAUAAGGUGCAGGUGAAGAUCCAG AACCCAACCGCCUGCACAGCCAAUGGCAGCUGUGACCCAUCCGUGACAAGGCAGGCAUACGCAGAUGUGA CCUUCUCUUUUACACAGUAUAGCACCGAUGAGGAGAGGGCCUUCGUGCGCACCGAGCUGGCCGCCCUGC UGGCAUCCCCUCUGCUGAUUGACGCUAUUGACCAGCUGAACCCUGCUUACUGAUAA (SEQ ID NO: 173) BG505_MD39_IC1 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGSGDPEFTKNALNVVKNDLIAK VDQLSGEQEVLRGELEAAKQAKVKLENRIKELEEELKRV** (SEQ ID NO: 177) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacga ggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgcc atcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggaggcagcggcagcg gcagcggggaccctgagtttaccaaaaatgctctgaatgtcgtcaaaaatgatctgattgctaaggtggaccagctgagcggagagcaggaggt gctgaggggcgagctggaggccgccaagcaggcaaaggtgaaactggaaaaccgaatcaaggaactggaagaagaactgaaaagagtctg ataa (SEQ ID NO: 175) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGAGGCAGCGGCAGCGGCAGCGGGGACCCUGAGUUUAC CAAAAAUGCUCUGAAUGUCGUCAAAAAUGAUCUGAUUGCUAAGGUGGACCAGCUGAGCGGAGAGCAGG AGGUGCUGAGGGGCGAGCUGGAGGCCGCCAAGCAGGCAAAGGUGAAACUGGAAAACCGAAUCAAGGAAC UGGAAGAAGAACUGAAAAGAGUCUGAUAA (SEQ ID NO: 176) BG505_MD39_IC2 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAENLWVTVYYGVPVWKDAETTLFCASDAKAYETEKHNVWATHACVPTDPNPQEIH LENVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLQCTNVTNNITDDMRGELKNCSFNMTTELR DKKQKVYSLFYRLDVVQINENQGNRSNNSNKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNGT GPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVIIRSENITNNAKNILVQLNTPVQINCTRPNNNTVKSIRIGPGQAF YYTGDIIGDIRQAHCNVSKATWNETLGKVVKQLRKHFGNNTIIRFAQSSGGDLEVTTHSFNCGGEFFYCNTSGLFNS TWISNTSVQGSNSTGSNDSITLPCRIKQIINMWQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPG GGDMRDNWRSELYKYKVVKIEPLGVAPTRCKRRVVGRRRRRRAVGIGAVSLGFLGAAGSTMGAASMTLTVQAR NLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNSSWSN RNLSEIWDNMTWLQWDKEISNYTQIIYGLLEESQNQQEKNEQDLLALDGGSGSGSGADPKKVLDKAKDQAENRV RELKQKLEELYKEARKLDLTQEMRRKLELRYIAAMLMAIGDIYNAIRQAKQEADKLKKAGLVNSQQLDELKRRLEEL KEEASRKARDYGREFQLKLEYGGGSGSGSGGKIEQILQKIEKILQKIEWILQKIEQILQG** (SEQ ID NO: 180) atggactggacatggattctgttcctggtcgctgccgctacaagagtgcattccgccgaaaacctgtgggtcaccgtctactatggagtgcccg tgtggaaggacgccgagactacgctgttctgcgccagcgatgccaaggcctacgagacagagaagcacaacgtgtgggcaacccacgcatgcgt gcctacagacccaaacccccaggagatccacctggagaatgtgacagaggagtttaacatgtggaagaacaatatggtggagcagatgcacg aggacatcatctccctgtgggatcagtctctgaagccctgcgtgaagctgacccctctgtgcgtgacactgcagtgtaccaacgtgacaaacaat atcaccgacgatatgcggggcgagctgaagaattgtagcttcaacatgaccacagagctgagggacaagaagcagaaggtgtactccctgtttt atagactggatgtggtgcagatcaatgagaaccagggcaatcggtctaacaatagcaacaaggagtaccgcctgatcaattgcaacacctccgcc atcacacaggcctgtcctaaggtgtctttcgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaaggataaga agtttaacggaaccggaccatgcccttccgtgtctaccgtgcagtgtacacacggcatcaagcctgtggtgtctacacagctgctgctgaatggc agcctggccgaggaggaagtgatcatcaggtctgagaacatcaccaacaatgccaagaatatcctggtgcagctgaacacaccagtgcagatca attgcacccggcccaacaataacacagtgaagtctatccgcatcggcccaggccaggccttttactataccggcgacatcatcggcgatatcaga caggcccactgtaatgtgagcaaggccacctggaacgagacactgggcaaggtggtgaagcagctgaggaagcacttcggcaataacaccat catcagatttgcacagagctccggcggcgacctggaggtgaccacacactccttcaattgcggcggcgagttcttttactgtaacacaagcggcc tgtttaattccacctggatctccaacacatctgtgcagggcagcaattccaccggcagcaacgattccatcacactgccatgccggatcaagcag atcatcaacatgtggcagcgcatcggccaggccatgtatgcccctcccatccagggcgtgatcagatgcgtgagcaatatcaccggcctgatcct gacacgcgacggcggctctaccaacagcaccacagagacattccggcccggcggcggcgacatgagggataactggagatctgagctgtaca agtataaggtggtgaagatcgagcctctgggagtggcaccaaccaggtgcaagaggagagtggtgggccggcgcaggagacggcgcgcagtg ggcatcggagccgtgtccctgggctttctgggagcagcaggctccacaatgggagcagcctctatgaccctgacagtgcaggccaggaatctgc tgagcggcatcgtgcagcagcagtccaacctgctgagagccccagagccccagcagcacctgctgaaggacacccactggggcatcaagcagc tgcaggccagggtgctggcagtggagcactatctgagagatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaa tgtgccctggaactctagctggtctaatcgcaacctgagcgagatctgggacaatatgacctggctgcagtgggataaggagatctccaactaca cacagatcatctatggcctgctggaagaatctcagaatcagcaggaaaagaatgaacaggatctgctggcactggatggcggaagcggaagtg gaagcggagccgaccccaagaaggtgctggataaagccaaagatcaggcagaaaatagagtcagggaactgaagcagaagctggaggagc tgtacaaggaggcccggaagctggacctgacccaggagatgaggagaaagctggagctgcgctacatcgccgccatgctgatggccatcggcg acatctataacgccatcaggcaggccaagcaggaggccgataagctgaagaaggccggcctggtgaatagccagcagctggacgagctgaag cggcgcctggaggagctgaaggaggaggccagcaggaaggccagagattacggcagggagttccagctgaagctggagtatggcggcggca gcggctccggctctggcggcaagatcgagcagatcctgcagaagatcgaaaagatcctgcagaagattgagtggattctgcagaagattgaac agatcctgcaggggtgataa (SEQ ID NO: 178) AUGGACUGGACAUGGAUUCUGUUCCUGGUCGCUGCCGCUACAAGAGUGCAUUCCGCCGAAAACCUGUG GGUCACCGUCUACUAUGGAGUGCCCGUGUGGAAGGACGCCGAGACUACGCUGUUCUGCGCCAGCGAUG CCAAGGCCUACGAGACAGAGAAGCACAACGUGUGGGCAACCCACGCAUGCGUGCCUACAGACCCAAACCC CCAGGAGAUCCACCUGGAGAAUGUGACAGAGGAGUUUAACAUGUGGAAGAACAAUAUGGUGGAGCAGA UGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGCCCUGCGUGAAGCUGACCCCUCUGUGCG UGACACUGCAGUGUACCAACGUGACAAACAAUAUCACCGACGAUAUGCGGGGCGAGCUGAAGAAUUGUA GCUUCAACAUGACCACAGAGCUGAGGGACAAGAAGCAGAAGGUGUACUCCCUGUUUUAUAGACUGGAU GUGGUGCAGAUCAAUGAGAACCAGGGCAAUCGGUCUAACAAUAGCAACAAGGAGUACCGCCUGAUCAAU UGCAACACCUCCGCCAUCACACAGGCCUGUCCUAAGGUGUCUUUCGAGCCUAUCCCAAUCCACUAUUGCG CCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAGGAUAAGAAGUUUAACGGAACCGGACCAUGCCCUUCCG UGUCUACCGUGCAGUGUACACACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCC UGGCCGAGGAGGAAGUGAUCAUCAGGUCUGAGAACAUCACCAACAAUGCCAAGAAUAUCCUGGUGCAGC UGAACACACCAGUGCAGAUCAAUUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCGCAUCGGCCC AGGCCAGGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGACAGGCCCACUGUAAUGUGAGCAA GGCCACCUGGAACGAGACACUGGGCAAGGUGGUGAAGCAGCUGAGGAAGCACUUCGGCAAUAACACCAU CAUCAGAUUUGCACAGAGCUCCGGCGGCGACCUGGAGGUGACCACACACUCCUUCAAUUGCGGCGGCGA GUUCUUUUACUGUAACACAAGCGGCCUGUUUAAUUCCACCUGGAUCUCCAACACAUCUGUGCAGGGCA GCAAUUCCACCGGCAGCAACGAUUCCAUCACACUGCCAUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCA GCGCAUCGGCCAGGCCAUGUAUGCCCCUCCCAUCCAGGGCGUGAUCAGAUGCGUGAGCAAUAUCACCGG CCUGAUCCUGACACGCGACGGCGGCUCUACCAACAGCACCACAGAGACAUUCCGGCCCGGCGGCGGCGAC AUGAGGGAUAACUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCUCUGGGAGUGG CACCAACCAGGUGCAAGAGGAGAGUGGUGGGCCGGCGCAGGAGACGGCGCGCAGUGGGCAUCGGAGCC GUGUCCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUCUAUGACCCUGACAGUGCA GGCCAGGAAUCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGAGCCCCAGAGCCCCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUA UCUGAGAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGC CCUGGAACUCUAGCUGGUCUAAUCGCAACCUGAGCGAGAUCUGGGACAAUAUGACCUGGCUGCAGUGG GAUAAGGAGAUCUCCAACUACACACAGAUCAUCUAUGGCCUGCUGGAAGAAUCUCAGAAUCAGCAGGAA AAGAAUGAACAGGAUCUGCUGGCACUGGAUGGCGGAAGCGGAAGUGGAAGCGGAGCCGACCCCAAGAA GGUGCUGGAUAAAGCCAAAGAUCAGGCAGAAAAUAGAGUCAGGGAACUGAAGCAGAAGCUGGAGGAGC UGUACAAGGAGGCCCGGAAGCUGGACCUGACCCAGGAGAUGAGGAGAAAGCUGGAGCUGCGCUACAUC GCCGCCAUGCUGAUGGCCAUCGGCGACAUCUAUAACGCCAUCAGGCAGGCCAAGCAGGAGGCCGAUAAG CUGAAGAAGGCCGGCCUGGUGAAUAGCCAGCAGCUGGACGAGCUGAAGCGGCGCCUGGAGGAGCUGAA GGAGGAGGCCAGCAGGAAGGCCAGAGAUUACGGCAGGGAGUUCCAGCUGAAGCUGGAGUAUGGCGGCG GCAGCGGCUCCGGCUCUGGCGGCAAGAUCGAGCAGAUCCUGCAGAAGAUCGAAAAGAUCCUGCAGAAGA UUGAGUGGAUUCUGCAGAAGAUUGAACAGAUCCUGCAGGGGUGAUAA (SEQ ID NO: 179) Global panel of trimers Parts of sequences Leader sequences IgE MDWTWILFLVAAATRVHS (SEQ ID NO: 7) Linkers Link 14 (same as MD3) GSHSGSGGSGSGGHA (SEQ ID NO: 13) There are no repeats in the gp120 or gp41 ecto between these sequences. I have highlighted them the same as the BG505_MD39. All of these are soluble IgE-gp120-linker-gp41 ecto (bold are glycan mutations) Full length sequences TRO11_AY835445_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSQGQLWVTVYYGVPVWKDASTTLFCASDAKAYDTEVHNVWATHACVPTDP NPQEVVLGNVTENFNMWKNNMVDQMHEDIISLWDQSLKPCVKLTPLCVTLNCTDNITNTNTNSSKNSS THSYNNSLEGEMKNCSFNITAGIRDKVKKEYALFYKLDVVPIEEDKDTNKTTYRLRSCNTSVITQACPKVTFE PIPIHYCAPAGFAILKCNDKKFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSENFTNNAKTII VQLNESIAINCTRPNNNTVRSIHIGPGRAFYYTGDIIGDIRQAHCNISRTEWNSTLRQIVTKLREQLGDPNKT IIFAQSSGGDTEITMHSFNCGGEFFYCNTTKLFNSTWNGNNTTESDSTGENITLPCRIKQIINLWQEVGKA MYAPPIKGQISCSSNITGLLLTRDGGNNNSSGPETFRPGGGNMKDNWRSELYKYKVIKIEPLGVAPTRCKR RVVGSHSGSGGSGSGGHAAVGTLGAMSLGFLGAAGSTMGAASVTLTVQARLLLSGIVQQQNNLLRAPE PQQHMLQDTHWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTNVPWNASWSNKSLNNIWENM TWMNWSREIDNYTDLIYILLEKSQIQQEKNNQSLLELD** (SEQ ID NO: 183) atggattggacttggattctgtttctggtcgctgctgctactcgggtgcattctcagggccagctgtgggtcactgtctactacggcgtg ccagtgtggaaggacgcctctaccacactgttttgcgccagcgacgccaaggcctacgatacagaggtgcacaacgtgtgggcaac acacgcatgcgtgccaaccgatccaaatccccaggaggtggtgctgggcaacgtgaccgagaacttcaatatgtggaagaacaata tggtggaccagatgcacgaggatatcatctctctgtgggaccagagcctgaagccctgcgtgaagctgacccctctgtgcgtgacact gaattgtaccgataacatcaccaacacaaataccaacagctccaagaactctagcacacactcctataacaattctctggagggcga gatgaagaattgttcctttaacatcaccgccggcatccgggacaaggtgaagaaggagtacgccctgttctataagctggatgtggtg cccatcgaggaggacaaggatacaaataagaccacataccggctgcgcagctgcaacacatccgtgatcacccaggcctgtcctaa ggtgacctttgagcctatcccaatccactattgcgccccagccggcttcgccatcctgaagtgtaatgacaagaagtttaacggcaca ggcccctgcaccaacgtgtctacagtgcagtgtacccacggcatcaggcctgtggtgtccacccagctgctgctgaatggctctctgg ccgaggaggaagtgatcatcagaagcgagaactttacaaacaatgccaagaccatcatcgtgcagctgaatgagtctatcgccatc aactgcacaaggccaaacaataacaccgtgagaagcatccacatcggaccaggaagggccttctactataccggcgacatcatcgg cgatatcaggcaggcccactgtaatatctccagaacagagtggaactctaccctgcggcagatcgtgacaaagctgcgcgagcagc tgggcgaccctaacaagaccatcatcttcgcccagtcctctggcggcgatacagagatcaccatgcactcctttaattgcggcggcga gttcttttactgtaacaccacaaagctgttcaattctacctggaacggcaataacaccacagagtccgactctacaggcgagaatatc accctgccatgccggatcaagcagatcatcaacctgtggcaggaagtgggcaaggccatgtatgcccctcccatcaagggccagat ctcctgtagctccaacatcacaggcctgctgctgacccgcgacggcggaaataacaattctagcggaccagagacattcaggcctgg cggcggcaatatgaaggataactggagaagcgagctgtacaagtataaagtgatcaagatcgagcctctgggagtggcaccaacc aggtgcaagaggagagtggtgggcagccactccggctctggcggcagcggctccggcggccacgcagcagtgggcacactgggcg ccatgagcctgggcttcctgggagcagcaggcagcaccatgggagcagcatccgtgacactgaccgtgcaggcaaggctgctgctg tccggcatcgtgcagcagcagaacaatctgctgagggcaccagagcctcagcagcacatgctgcaggacacacactggggcatca agcagctgcaggcccgggtgctggcagtggagcactacctgcgcgatcagcagctgctgggcatctggggctgtagcggcaagctg atctgctgtaccaatgtgccttggaacgcctcttggagcaataagagcctgaacaatatctgggagaatatgacatggatgaactggt ccagagagatcgacaactacaccgatctgatctatatcctgctggagaagtcacagattcagcaggagaagaacaatcagagcctg ctggaactggattgataa (SEQ ID NO: 181) AUGGAUUGGACUUGGAUUCUGUUUCUGGUCGCUGCUGCUACUCGGGUGCAUUCUCAGGGCCA GCUGUGGGUCACUGUCUACUACGGCGUGCCAGUGUGGAAGGACGCCUCUACCACACUGUUUUG CGCCAGCGACGCCAAGGCCUACGAUACAGAGGUGCACAACGUGUGGGCAACACACGCAUGCGUG CCAACCGAUCCAAAUCCCCAGGAGGUGGUGCUGGGCAACGUGACCGAGAACUUCAAUAUGUGGA AGAACAAUAUGGUGGACCAGAUGCACGAGGAUAUCAUCUCUCUGUGGGACCAGAGCCUGAAGC CCUGCGUGAAGCUGACCCCUCUGUGCGUGACACUGAAUUGUACCGAUAACAUCACCAACACAAA UACCAACAGCUCCAAGAACUCUAGCACACACUCCUAUAACAAUUCUCUGGAGGGCGAGAUGAAG AAUUGUUCCUUUAACAUCACCGCCGGCAUCCGGGACAAGGUGAAGAAGGAGUACGCCCUGUUC UAUAAGCUGGAUGUGGUGCCCAUCGAGGAGGACAAGGAUACAAAUAAGACCACAUACCGGCUGC GCAGCUGCAACACAUCCGUGAUCACCCAGGCCUGUCCUAAGGUGACCUUUGAGCCUAUCCCAAU CCACUAUUGCGCCCCAGCCGGCUUCGCCAUCCUGAAGUGUAAUGACAAGAAGUUUAACGGCACA GGCCCCUGCACCAACGUGUCUACAGUGCAGUGUACCCACGGCAUCAGGCCUGUGGUGUCCACCC AGCUGCUGCUGAAUGGCUCUCUGGCCGAGGAGGAAGUGAUCAUCAGAAGCGAGAACUUUACAA ACAAUGCCAAGACCAUCAUCGUGCAGCUGAAUGAGUCUAUCGCCAUCAACUGCACAAGGCCAAA CAAUAACACCGUGAGAAGCAUCCACAUCGGACCAGGAAGGGCCUUCUACUAUACCGGCGACAUC AUCGGCGAUAUCAGGCAGGCCCACUGUAAUAUCUCCAGAACAGAGUGGAACUCUACCCUGCGGC AGAUCGUGACAAAGCUGCGCGAGCAGCUGGGCGACCCUAACAAGACCAUCAUCUUCGCCCAGUC CUCUGGCGGCGAUACAGAGAUCACCAUGCACUCCUUUAAUUGCGGCGGCGAGUUCUUUUACUG UAACACCACAAAGCUGUUCAAUUCUACCUGGAACGGCAAUAACACCACAGAGUCCGACUCUACAG GCGAGAAUAUCACCCUGCCAUGCCGGAUCAAGCAGAUCAUCAACCUGUGGCAGGAAGUGGGCAA GGCCAUGUAUGCCCCUCCCAUCAAGGGCCAGAUCUCCUGUAGCUCCAACAUCACAGGCCUGCUG CUGACCCGCGACGGCGGAAAUAACAAUUCUAGCGGACCAGAGACAUUCAGGCCUGGCGGCGGCA AUAUGAAGGAUAACUGGAGAAGCGAGCUGUACAAGUAUAAAGUGAUCAAGAUCGAGCCUCUGG GAGUGGCACCAACCAGGUGCAAGAGGAGAGUGGUGGGCAGCCACUCCGGCUCUGGCGGCAGCG GCUCCGGCGGCCACGCAGCAGUGGGCACACUGGGCGCCAUGAGCCUGGGCUUCCUGGGAGCAGC AGGCAGCACCAUGGGAGCAGCAUCCGUGACACUGACCGUGCAGGCAAGGCUGCUGCUGUCCGGC AUCGUGCAGCAGCAGAACAAUCUGCUGAGGGCACCAGAGCCUCAGCAGCACAUGCUGCAGGACA CACACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAGUGGAGCACUACCUGCGCGAUCA GCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUACCAAUGUGCCUUGGAA CGCCUCUUGGAGCAAUAAGAGCCUGAACAAUAUCUGGGAGAAUAUGACAUGGAUGAACUGGUC CAGAGAGAUCGACAACUACACCGAUCUGAUCUAUAUCCUGCUGGAGAAGUCACAGAUUCAGCAG GAGAAGAACAAUCAGAGCCUGCUGGAACUGGAUUGAUAA (SEQ ID NO: 182) X2278_FJ817366_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSTNNLWVTVYYGVPVWKEATTTLFCASEAKAYDTEVHNIWATHACVPTDPN PQEMELKNVTENFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLDCTNINSTNSTNNTSSNSK MEETIGVIKNCSFNVTTNIRDKVKKENALFYSLDLVSIGNSNTSYRLISCNTSIITQACPKVSFDPIPIHYCAPA GFAILKCRDKKFNGTGPCRNVSSVQCTHGIRPVVSTQLLLNGSLAEEEIIIRSANLTDNAKTIIIQLNETIQINC TRPNNNTVRSIPIGPGRTFYYTGDIIGDIRKAYCNISATKWNNTLRQIAEKLREKFNKTIIFAQSSGGDPEVVR HTFNCGGEFFYCNSSQLFNSTWYSNGTSNGGLNNSANITLPCRIKQIINLWQEVGKAMYAPPIKGVINCLS NITGIILTRDGGENNGTTETFRPGGGDMRDNWRSELYKYKVVKIEPLGIAPTKCKRRVVGSHSGSGGSGSG GHAAVGLGAVSLGFLGLAGSTMGAASVTLTVQARLLLSGIVQQQNNLLRAPEPQQQLLQDTHWGIKQL QARVLALEHYLKDQQLLGIWGCSGKLICCTTVPWNASWSNKSYNQIWNNMTWMNWSREIDNYTNLIY NLIEESQSQQEKNNLSLLQLD** (SEQ ID NO: 186) atggactggacctggattctgttcctggtcgccgctgctacaagagtgcattctacaaataacctgtgggtgactgtctactatggagt gcccgtgtggaaggaggccaccacaaccctgttctgcgccagcgaggccaaggcctacgacacagaggtgcacaacatctgggcc acccacgcctgcgtgcctacagatccaaacccccaggagatggagctgaagaatgtgaccgagaacttcaacatgtggaagaaca atatggtggagcagatgcacgaggacatcatcagcctgtgggatcagtccctgaagccctgcgtgaagctgacacctctgtgcgtga ccctggattgtacaaatatcaacagcacaaactccaccaacaatacaagctccaattctaagatggaggagacaatcggcgtgatca agaattgtagcttcaacgtgacaaccaatatccgggacaaggtgaagaaggagaacgccctgttttactctctggatctggtgagcat cggcaattctaacaccagctatcgcctgatctcctgcaatacctctatcatcacacaggcctgtccaaaggtgagcttcgaccctatcc caatccactactgcgcaccagcaggattcgcaatcctgaagtgtagggataagaagtttaacggcaccggcccttgcagaaacgtga gcagcgtgcagtgtacacacggcatcaggccagtggtgagcacccagctgctgctgaacggctccctggcagaggaggagatcatc atcagatccgccaacctgaccgacaatgccaagacaatcatcatccagctgaacgagacaatccagatcaattgcacaaggcccaa caataacaccgtgagaagcatcccaatcggccccggccggaccttttactatacaggcgacatcatcggcgatatccgcaaggccta ctgtaacatctccgccaccaagtggaataacacactgcggcagatcgccgagaagctgcgcgagaagttcaacaagacaatcatct ttgcccagtcctctggcggcgatccagaggtggtgaggcacaccttcaattgcggcggcgagttcttttactgtaacagctcccagctg tttaatagcacatggtattccaacggcacctctaatggcggcctgaataacagcgccaacatcaccctgccctgcagaatcaagcag atcatcaatctgtggcaggaagtgggcaaggccatgtatgcccctcccatcaagggcgtgatcaactgtctgtccaatatcaccggca tcatcctgacaagggacggcggcgagaataacggcacaaccgagacattcagacccggcggcggcgacatgagggataactggc gctctgagctgtacaagtataaggtggtgaagatcgagcctctgggcatcgccccaaccaagtgcaagaggagagtggtgggctctc acagcggctccggcggctctggcagcggcggccacgcagcagtgggcctgggagccgtgtctctgggctttctgggcctggcaggct ccacaatgggagcagcctctgtgacactgaccgtgcaggcaaggctgctgctgagcggcatcgtgcagcagcagaataacctgctg agggcaccagagcctcagcagcagctgctgcaggacacccactggggcatcaagcagctgcaggcccgggtgctggccctggagc actacctgaaggatcagcagctgctgggcatctggggctgttccggcaagctgatctgctgtacaaccgtgccatggaacgcctcctg gtctaacaagtcctataatcagatctggaataacatgacatggatgaactggagcagggagatcgacaattacaccaacctgatcta taatctgattgaagagtcacagtcacagcaggaaaagaacaacctgagcctgctgcagctggactgataa (SEQ ID NO: 188) AUGGACUGGACCUGGAUUCUGUUCCUGGUCGCCGCUGCUACAAGAGUGCAUUCUACAAAUAAC CUGUGGGUGACUGUCUACUAUGGAGUGCCCGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCAGCGAGGCCAAGGCCUACGACACAGAGGUGCACAACAUCUGGGCCACCCACGCCUGCGUGCC UACAGAUCCAAACCCCCAGGAGAUGGAGCUGAAGAAUGUGACCGAGAACUUCAACAUGUGGAAG AACAAUAUGGUGGAGCAGAUGCACGAGGACAUCAUCAGCCUGUGGGAUCAGUCCCUGAAGCCC UGCGUGAAGCUGACACCUCUGUGCGUGACCCUGGAUUGUACAAAUAUCAACAGCACAAACUCCA CCAACAAUACAAGCUCCAAUUCUAAGAUGGAGGAGACAAUCGGCGUGAUCAAGAAUUGUAGCUU CAACGUGACAACCAAUAUCCGGGACAAGGUGAAGAAGGAGAACGCCCUGUUUUACUCUCUGGAU CUGGUGAGCAUCGGCAAUUCUAACACCAGCUAUCGCCUGAUCUCCUGCAAUACCUCUAUCAUCA CACAGGCCUGUCCAAAGGUGAGCUUCGACCCUAUCCCAAUCCACUACUGCGCACCAGCAGGAUU CGCAAUCCUGAAGUGUAGGGAUAAGAAGUUUAACGGCACCGGCCCUUGCAGAAACGUGAGCAG CGUGCAGUGUACACACGGCAUCAGGCCAGUGGUGAGCACCCAGCUGCUGCUGAACGGCUCCCUG GCAGAGGAGGAGAUCAUCAUCAGAUCCGCCAACCUGACCGACAAUGCCAAGACAAUCAUCAUCCA GCUGAACGAGACAAUCCAGAUCAAUUGCACAAGGCCCAACAAUAACACCGUGAGAAGCAUCCCAA UCGGCCCCGGCCGGACCUUUUACUAUACAGGCGACAUCAUCGGCGAUAUCCGCAAGGCCUACUG UAACAUCUCCGCCACCAAGUGGAAUAACACACUGCGGCAGAUCGCCGAGAAGCUGCGCGAGAAG UUCAACAAGACAAUCAUCUUUGCCCAGUCCUCUGGCGGCGAUCCAGAGGUGGUGAGGCACACCU UCAAUUGCGGCGGCGAGUUCUUUUACUGUAACAGCUCCCAGCUGUUUAAUAGCACAUGGUAUU CCAACGGCACCUCUAAUGGCGGCCUGAAUAACAGCGCCAACAUCACCCUGCCCUGCAGAAUCAAG CAGAUCAUCAAUCUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCCCCUCCCAUCAAGGGCGUG AUCAACUGUCUGUCCAAUAUCACCGGCAUCAUCCUGACAAGGGACGGCGGCGAGAAUAACGGCA CAACCGAGACAUUCAGACCCGGCGGCGGCGACAUGAGGGAUAACUGGCGCUCUGAGCUGUACAA GUAUAAGGUGGUGAAGAUCGAGCCUCUGGGCAUCGCCCCAACCAAGUGCAAGAGGAGAGUGGU GGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCCACGCAGCAGUGGGCCUGGGAGC CGUGUCUCUGGGCUUUCUGGGCCUGGCAGGCUCCACAAUGGGAGCAGCCUCUGUGACACUGAC CGUGCAGGCAAGGCUGCUGCUGAGCGGCAUCGUGCAGCAGCAGAAUAACCUGCUGAGGGCACCA GAGCCUCAGCAGCAGCUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGC UGGCCCUGGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGC UGAUCUGCUGUACAACCGUGCCAUGGAACGCCUCCUGGUCUAACAAGUCCUAUAAUCAGAUCUG GAAUAACAUGACAUGGAUGAACUGGAGCAGGGAGAUCGACAAUUACACCAACCUGAUCUAUAAU CUGAUUGAAGAGUCACAGUCACAGCAGGAAAAGAACAACCUGAGCCUGCUGCAGCUGGACUGAU AA (SEQ ID NO: 189) 398F1_HM215312_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSMGNLWVTVYYGVPVWKDAETTLFCASDAKAYHTEVHNVWATHACVPTD PNPQEINLENVTEEFNMWKNKMVEQMHEDIISLWDQSLKPCVQLTPLCVTLDCQYNVTNINSTSDMAR EINNCSYNITTELRDREQKVYSLFYRSDIVQMNSDNSSKYRLINCNTSAIKQACPKVTFEPIPIHYCAPAGFAIL KCKDKEFNGTGPCKNVSTVQCTHGIKPVVSTQLLLNGSLAEEKVIIRSENITDNAKNIIVQLKEPVKINCTRP NNNTVKSVRIGPGQTFYYTGEIIGDIRQAHCNVSKAHWENTLQEVANQLKLMIHSNKTIIFANSSGGDLEIT THSFNCGGEFFYCYTSGLFNYTFNDTSTNSTESKSNDTITLQCRIKQIINMWQRAGQAVYAPPIPGIIRCESN ITGLILTRDGGNNNSNTNETFRPGGGDMRDNWRSELYRYKVVKIEPIGVAPTTCKRRVVGSHSGSGGSGS GGHAAVGIGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQL KARVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSLGEIWDNMTWLNWSKEIENYTQIIYELI EESQNQQEKNNQSLLALD** (SEQ ID NO: 189) atggactggacttggattctgtttctggtcgcagccgcaactagagtgcatagcatgggcaacctgtgggtcaccgtgtattacggggt gccagtgtggaaggacgccgagactacgctgttctgcgcctccgatgccaaggcctaccacacagaggtgcacaacgtgtgggcaa cccacgcatgcgtgccaacagacccaaatccccaggagatcaacctggagaatgtgaccgaggagtttaacatgtggaagaataag atggtggagcagatgcacgaggacatcatctccctgtgggatcagtctctgaagccttgcgtgcagctgaccccactgtgcgtgacac tggactgtcagtacaacgtgaccaacatcaatagcacatccgatatggccagggagatcaacaattgtagctataatatcaccacag agctgcgggatcgcgagcagaaagtgtacagcctgttctataggtccgacatcgtgcagatgaactccgataatagctccaagtaca gactgatcaactgcaatacctctgccatcaagcaggcctgtccaaaggtgacatttgagcctatcccaatccactattgcgcaccagc aggattcgcaatcctgaagtgtaaggacaaggagtttaacggcaccggcccttgcaagaacgtgagcaccgtgcagtgtacacacg gcatcaagccagtggtgagcacacagctgctgctgaacggctccctggccgaggagaaagtgatcatccggtctgagaatatcacc gataacgccaagaatatcatcgtgcagctgaaggagcccgtgaagatcaactgcacccggcctaacaataacacagtgaagtccgt gcgcatcggccctggccagaccttctactatacaggcgagatcatcggcgacatccgccaggcccactgtaacgtgtctaaggccca ctgggagaacaccctgcaggaggtggccaatcagctgaagctgatgatccacagcaacaagacaatcatcttcgccaattctagcg gcggcgatctggagatcaccacacactcttttaactgcggcggcgagttcttttactgttataccagcggcctgttcaactacaccttca acgacaccagcacaaactccaccgagtctaagagcaatgataccatcacactgcagtgcaggatcaagcagatcatcaacatgtgg cagagagcaggacaggccgtgtatgcccctcccatccccggcatcatccggtgtgagagcaatatcaccggcctgatcctgacacgc gacggcggaaataacaattccaacaccaatgagacattcaggcccggcggcggcgacatgagggataactggagatctgagctgt acagatataaggtggtgaagatcgagccaatcggcgtggcccccaccacatgcaagaggagagtggtgggctcccactctggcagc ggcggctccggctctggcggccacgcagccgtgggcatcggagccgtgagcctgggctttctgggagcagcaggctctaccatggg agcagccagcatcaccctgacagtgcaggcaaggcagctgctgtccggaatcgtgcagcagcagtctaacctgctgagggcaccag agcctcagcagcacctgctgaaggacacccactggggcatcaagcagctgaaggccagggtgctggccgtggagcactacctgaa ggatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccaacgtgccctggaattcctcttggtctaacaag agcctgggcgagatctgggacaacatgacctggctgaattggtccaaggagatcgagaattacacacagatcatctatgagctgatt gaagagtcacagaaccagcaggagaaaaacaaccagagcctgctggcactggattgataa (SEQ ID NO: 187) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGCCGCAACUAGAGUGCAUAGCAUGGGCAAC CUGUGGGUCACCGUGUAUUACGGGGUGCCAGUGUGGAAGGACGCCGAGACUACGCUGUUCUG CGCCUCCGAUGCCAAGGCCUACCACACAGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUG CCAACAGACCCAAAUCCCCAGGAGAUCAACCUGGAGAAUGUGACCGAGGAGUUUAACAUGUGGA AGAAUAAGAUGGUGGAGCAGAUGCACGAGGACAUCAUCUCCCUGUGGGAUCAGUCUCUGAAGC CUUGCGUGCAGCUGACCCCACUGUGCGUGACACUGGACUGUCAGUACAACGUGACCAACAUCAA UAGCACAUCCGAUAUGGCCAGGGAGAUCAACAAUUGUAGCUAUAAUAUCACCACAGAGCUGCGG GAUCGCGAGCAGAAAGUGUACAGCCUGUUCUAUAGGUCCGACAUCGUGCAGAUGAACUCCGAU AAUAGCUCCAAGUACAGACUGAUCAACUGCAAUACCUCUGCCAUCAAGCAGGCCUGUCCAAAGG UGACAUUUGAGCCUAUCCCAAUCCACUAUUGCGCACCAGCAGGAUUCGCAAUCCUGAAGUGUAA GGACAAGGAGUUUAACGGCACCGGCCCUUGCAAGAACGUGAGCACCGUGCAGUGUACACACGGC AUCAAGCCAGUGGUGAGCACACAGCUGCUGCUGAACGGCUCCCUGGCCGAGGAGAAAGUGAUCA UCCGGUCUGAGAAUAUCACCGAUAACGCCAAGAAUAUCAUCGUGCAGCUGAAGGAGCCCGUGAA GAUCAACUGCACCCGGCCUAACAAUAACACAGUGAAGUCCGUGCGCAUCGGCCCUGGCCAGACC UUCUACUAUACAGGCGAGAUCAUCGGCGACAUCCGCCAGGCCCACUGUAACGUGUCUAAGGCCC ACUGGGAGAACACCCUGCAGGAGGUGGCCAAUCAGCUGAAGCUGAUGAUCCACAGCAACAAGAC AAUCAUCUUCGCCAAUUCUAGCGGCGGCGAUCUGGAGAUCACCACACACUCUUUUAACUGCGGC GGCGAGUUCUUUUACUGUUAUACCAGCGGCCUGUUCAACUACACCUUCAACGACACCAGCACAA ACUCCACCGAGUCUAAGAGCAAUGAUACCAUCACACUGCAGUGCAGGAUCAAGCAGAUCAUCAA CAUGUGGCAGAGAGCAGGACAGGCCGUGUAUGCCCCUCCCAUCCCCGGCAUCAUCCGGUGUGAG AGCAAUAUCACCGGCCUGAUCCUGACACGCGACGGCGGAAAUAACAAUUCCAACACCAAUGAGAC AUUCAGGCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUCUGAGCUGUACAGAUAUAAGGU GGUGAAGAUCGAGCCAAUCGGCGUGGCCCCCACCACAUGCAAGAGGAGAGUGGUGGGCUCCCAC UCUGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCAGCCGUGGGCAUCGGAGCCGUGAGCCUG GGCUUUCUGGGAGCAGCAGGCUCUACCAUGGGAGCAGCCAGCAUCACCCUGACAGUGCAGGCAA GGCAGCUGCUGUCCGGAAUCGUGCAGCAGCAGUCUAACCUGCUGAGGGCACCAGAGCCUCAGCA GCACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGAAGGCCAGGGUGCUGGCCGUGGA GCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUG UACCAACGUGCCCUGGAAUUCCUCUUGGUCUAACAAGAGCCUGGGCGAGAUCUGGGACAACAU GACCUGGCUGAAUUGGUCCAAGGAGAUCGAGAAUUACACACAGAUCAUCUAUGAGCUGAUUGA AGAGUCACAGAACCAGCAGGAGAAAAACAACCAGAGCCUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 188) 246F3_HM215279_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSMQDLWVTVYYGVPVWKDAKTTLFCASDAKAYEKEVHNVWATHACVPTD PNPQEIVMANVTEEFNMWKNNMVEQMHEDIISLWDQSLKPCVKLTPLCVTLDCKDYNYSITNNSTGME GEIKNCSYNITTELRDKRQKVYSLFYRLDVVQINDSNDRNNSQYRLINCNTTTMTQACPKVTFDPIPIHYCA PAGFAILKCNNKTFNGKGPCNNVSSVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTDNVKTIIVHLNESVE INCTRPNNNTVKSVRIGPGQTFYYTGDIIGNIRQAHCTVNKTEWNTALTRVSKKLKEYFPNKTIAFQPSSGG DLEITTFSFNCRGEFFYCNTSDLFNGTFNETSGQFNSTFNSTLQCRIKQIINMWQEVGQAMYAPPIAGSITC ISNITGLILTRDGGNTNSTKETFRPGGGNMRDNWRSELYKYKVVKIEPLGVAPTKCRRRVVGSHSGSGGSG SGGHAAVGIGAVSIGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLKDTHWGIKQL QARVLAVEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNKSQDEIWDNMTWLNWSKEISNYTQIIYNL IEESQTQQELNNRSLLALD** (SEQ ID NO: 192) atggactggacttggattctgtttctggtcgcagccgctactcgggtgcactctatgcaggacctgtgggtgaccgtctattatggggtg ccagtgtggaaggacgccaagaccacactgttctgcgcctccgatgccaaggcctacgagaaggaggtgcacaacgtgtgggcaac ccacgcatgcgtgccaacagacccaaacccccaggagatcgtgatggccaatgtgaccgaggagtttaacatgtggaagaacaata tggtggagcagatgcacgaggacatcatctctctgtgggatcagagcctgaagccttgcgtgaagctgaccccactgtgcgtgacac tggactgtaaggattacaactattccatcaccaacaattctacaggcatggagggcgagatcaagaattgttcttataacatcaccac agagctgcgcgacaagaggcagaaagtgtacagcctgttctatcgcctggatgtggtgcagatcaatgactctaacgatcgcaacaa tagccagtacaggctgatcaattgcaacaccacaaccatgacccaggcctgtcctaaggtgacatttgaccctatcccaatccactat tgcgccccagccggcttcgccatcctgaagtgtaacaataagacctttaatggcaagggcccctgcaacaatgtgagctccgtgcagt gtacccacggcatcaagcctgtggtgtctacacagctgctgctgaacggcagcctggccgagaaggagatcatcatcaggagcgag aatctgaccgacaacgtgaagacaatcatcgtgcacctgaatgagagcgtggagatcaactgcaccagaccaaacaataacacagt gaagtccgtgcggatcggaccaggacagaccttctactatacaggcgatatcatcggcaatatccgccaggcccactgtaccgtgaa taagacagagtggaacacagccctgaccagggtgagcaagaagctgaaggagtacttccccaacaagaccatcgcctttcagcctt ctagcggcggcgacctggagatcacaaccttctcctttaattgcagaggcgagttcttttattgtaacacatccgatctgttcaatggca cctttaacgagacatctggccagttcaattccacctttaactctacactgcagtgccggatcaagcagatcatcaatatgtggcagga agtgggacaggcaatgtacgcccctcccatcgcaggcagcatcacctgtatctccaacatcaccggcctgatcctgacacgcgacgg cggaaatacaaactccaccaaggagacattcaggcctggcggcggcaatatgagagataactggcggtctgagctgtacaagtata aggtggtgaagatcgagccactgggagtggcaccaaccaagtgcaggagacgggtggtgggcagccactccggctctggcggcag cggctccggcggccacgcagcagtgggcatcggcgccgtgtctatcggctttctgggagcagcaggctccaccatgggagcagcctc tatcacactgaccgtgcaggccagacagctgctgagcggcatcgtgcagcagcagtccaacctgctgagggcaccagagcctcagc agcacctgctgaaggacacccactggggcatcaagcagctgcaggccagggtgctggcagtggagcactacctgaaggatcagca gctgctgggcatctggggctgtagcggcaagctgatctgctgtacaaatgtgccctggaactcctcttggtctaacaagagccaggac gagatctgggataatatgacctggctgaactggagcaaggagatctccaattacacacagatcatctataacctgattgaagaatca cagactcagcaggaactgaataataggtcactgctggcactggattgataa (SEQ ID NO: 190) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGCCGCUACUCGGGUGCACUCUAUGCAGGAC CUGUGGGUGACCGUCUAUUAUGGGGUGCCAGUGUGGAAGGACGCCAAGACCACACUGUUCUGC GCCUCCGAUGCCAAGGCCUACGAGAAGGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUGC CAACAGACCCAAACCCCCAGGAGAUCGUGAUGGCCAAUGUGACCGAGGAGUUUAACAUGUGGAA GAACAAUAUGGUGGAGCAGAUGCACGAGGACAUCAUCUCUCUGUGGGAUCAGAGCCUGAAGCC UUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGACUGUAAGGAUUACAACUAUUCCAUCACC AACAAUUCUACAGGCAUGGAGGGCGAGAUCAAGAAUUGUUCUUAUAACAUCACCACAGAGCUGC GCGACAAGAGGCAGAAAGUGUACAGCCUGUUCUAUCGCCUGGAUGUGGUGCAGAUCAAUGACU CUAACGAUCGCAACAAUAGCCAGUACAGGCUGAUCAAUUGCAACACCACAACCAUGACCCAGGCC UGUCCUAAGGUGACAUUUGACCCUAUCCCAAUCCACUAUUGCGCCCCAGCCGGCUUCGCCAUCC UGAAGUGUAACAAUAAGACCUUUAAUGGCAAGGGCCCCUGCAACAAUGUGAGCUCCGUGCAGU GUACCCACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAACGGCAGCCUGGCCGAGAA GGAGAUCAUCAUCAGGAGCGAGAAUCUGACCGACAACGUGAAGACAAUCAUCGUGCACCUGAAU GAGAGCGUGGAGAUCAACUGCACCAGACCAAACAAUAACACAGUGAAGUCCGUGCGGAUCGGAC CAGGACAGACCUUCUACUAUACAGGCGAUAUCAUCGGCAAUAUCCGCCAGGCCCACUGUACCGU GAAUAAGACAGAGUGGAACACAGCCCUGACCAGGGUGAGCAAGAAGCUGAAGGAGUACUUCCCC AACAAGACCAUCGCCUUUCAGCCUUCUAGCGGCGGCGACCUGGAGAUCACAACCUUCUCCUUUA AUUGCAGAGGCGAGUUCUUUUAUUGUAACACAUCCGAUCUGUUCAAUGGCACCUUUAACGAGA CAUCUGGCCAGUUCAAUUCCACCUUUAACUCUACACUGCAGUGCCGGAUCAAGCAGAUCAUCAA UAUGUGGCAGGAAGUGGGACAGGCAAUGUACGCCCCUCCCAUCGCAGGCAGCAUCACCUGUAUC UCCAACAUCACCGGCCUGAUCCUGACACGCGACGGCGGAAAUACAAACUCCACCAAGGAGACAUU CAGGCCUGGCGGCGGCAAUAUGAGAGAUAACUGGCGGUCUGAGCUGUACAAGUAUAAGGUGGU GAAGAUCGAGCCACUGGGAGUGGCACCAACCAAGUGCAGGAGACGGGUGGUGGGCAGCCACUC CGGCUCUGGCGGCAGCGGCUCCGGCGGCCACGCAGCAGUGGGCAUCGGCGCCGUGUCUAUCGG CUUUCUGGGAGCAGCAGGCUCCACCAUGGGAGCAGCCUCUAUCACACUGACCGUGCAGGCCAGA CAGCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGGGCACCAGAGCCUCAGCAGC ACCUGCUGAAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCA CUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUAC AAAUGUGCCCUGGAACUCCUCUUGGUCUAACAAGAGCCAGGACGAGAUCUGGGAUAAUAUGAC CUGGCUGAACUGGAGCAAGGAGAUCUCCAAUUACACACAGAUCAUCUAUAACCUGAUUGAAGAA UCACAGACUCAGCAGGAACUGAAUAAUAGGUCACUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 191) CE0217_FJ443575_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSAKDMWVTVYYGVPVWREAKTTLFCASDAKAYEREVHNVWATHACVPTDP NPQERVLENVTENFNMWKNNMVDQMHEDIISLWDESLKPCIKLTPLCVTLNCGNAIVNESTIEGMKNCS FNVTTELKDKKKKEYALFYKLDVVPLNGENNNSNSKNFSEYRLINCNTSTITQACPKVSFDPIPIHYCAPAGF AILKCNNETFNGTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTNNAKIIIVHLNNPVKIICTR PGNNTVKSMRIGPGQTFYYTGDIIGDIRRAYCNISEKTWYDTLKNVSDKFQEHFPNASIEFKPSAGGDLEIT THSFNCRGEFFYCDTSELFNGTYNNSTYNSSNNITLQCKIKQIINMWQGVGRAMYAPPIAGNITCESNITG LLLTRDGGNNKSTPETFRPGGGDMRDNWRSELYKYKVVEIKPLGIAPTKCKRRVVGSHSGSGGSGSGGHA AVGMGAVSLGFLGAAGSTMGAASLTLTVQARQLLSGIVQQQNNLLRAPEPQQHMLQDTHWGIKQLQA RVLAIEHYLTDQQLLGIWGCSGKLICCTNVPWNNSWSNKSYEDIWGRNMTWMNWSREINNYTNTIYRL LEKSQNQQEKNNKSLLELD** (SEQ ID NO: 195) atggactggacttggattctgtttctggtcgccgccgcaactcgcgtgcattcagcaaaagatatgtgggtcaccgtctattatggagt gcccgtgtggcgggaggccaagaccacactgttttgcgcaagcgacgcaaaggcatacgagagggaggtgcacaacgtgtgggcc acacacgcctgcgtgccaaccgatccaaatccccaggagagagtgctggagaacgtgaccgagaatttcaacatgtggaagaaca atatggtggaccagatgcacgaggatatcatctctctgtgggacgagagcctgaagccctgcatcaagctgacacctctgtgcgtga ccctgaattgtggcaacgccatcgtgaatgagtccaccatcgagggcatgaagaattgttcttttaacgtgaccacagagctgaagg acaagaagaagaaggagtacgccctgttctataagctggatgtggtgcccctgaacggcgagaacaacaactctaacagcaagaa ctttagcgagtacaggctgatcaattgcaacacctccacaatcacccaggcctgtcccaaggtgtctttcgatcctatcccaatccact attgcgcccctgccggcttcgccatcctgaagtgtaataacgagacattcaacggcaccggcccatgcaataacgtgtccacagtgc agtgtacccacggcatcaagcccgtggtgtctacacagctgctgctgaatggcagcctggccgagaaggagatcatcatcaggtctg agaacctgaccaataacgccaagatcatcatcgtgcacctgaataacccagtgaagatcatctgcacaaggcccggcaataacacc gtgaagagcatgagaatcggccctggccagacattctactataccggcgacatcatcggcgatatcaggagagcctactgtaacatc tctgagaagacatggtatgacaccctgaagaatgtgagcgataagttccaggagcactttcctaacgcctccatcgagttcaagccat ctgccggcggcgacctggagatcaccacacactcctttaattgcaggggcgagttcttttactgtgatacaagcgagctgttcaatgg cacatacaataactccacctataacagctccaataacatcaccctgcagtgcaagatcaagcagatcatcaacatgtggcagggcgt gggcagagccatgtatgcccctcccatcgccggcaatatcacctgtgagagcaacatcacaggcctgctgctgacccgggacggcg gaaataacaagtccacaccagagacattcaggcccggcggcggcgacatgagggataactggagaagcgagctgtacaagtataa ggtggtggagatcaagcctctgggcatcgccccaacaaagtgcaagaggagggtggtgggctcccactctggcagcggcggctccg gctctggcggccacgcagccgtgggcatgggcgccgtgtctctgggcttcctgggagcagcaggcagcaccatgggagcagcatcc ctgacactgaccgtgcaggcaaggcagctgctgagcggcatcgtgcagcagcagaataacctgctgagagcccccgagcctcagca gcacatgctgcaggacacacactggggcatcaagcagctgcaggcccgggtgctggcaatcgagcactacctgacagatcagcag ctgctgggcatctggggctgttccggcaagctgatctgctgtaccaatgtgccctggaataacagctggtccaacaagtcctatgagg atatctggggccggaatatgacctggatgaactggagcagggagatcaacaactacacaaacaccatctatcgcctgctggaaaag tcacagaatcagcaggagaagaataataagtcactgctggaactggactgataa (SEQ ID NO: 193) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCCGCCGCAACUCGCGUGCAUUCAGCAAAAGAU AUGUGGGUCACCGUCUAUUAUGGAGUGCCCGUGUGGCGGGAGGCCAAGACCACACUGUUUUGC GCAAGCGACGCAAAGGCAUACGAGAGGGAGGUGCACAACGUGUGGGCCACACACGCCUGCGUGC CAACCGAUCCAAAUCCCCAGGAGAGAGUGCUGGAGAACGUGACCGAGAAUUUCAACAUGUGGAA GAACAAUAUGGUGGACCAGAUGCACGAGGAUAUCAUCUCUCUGUGGGACGAGAGCCUGAAGCC CUGCAUCAAGCUGACACCUCUGUGCGUGACCCUGAAUUGUGGCAACGCCAUCGUGAAUGAGUC CACCAUCGAGGGCAUGAAGAAUUGUUCUUUUAACGUGACCACAGAGCUGAAGGACAAGAAGAA GAAGGAGUACGCCCUGUUCUAUAAGCUGGAUGUGGUGCCCCUGAACGGCGAGAACAACAACUC UAACAGCAAGAACUUUAGCGAGUACAGGCUGAUCAAUUGCAACACCUCCACAAUCACCCAGGCC UGUCCCAAGGUGUCUUUCGAUCCUAUCCCAAUCCACUAUUGCGCCCCUGCCGGCUUCGCCAUCC UGAAGUGUAAUAACGAGACAUUCAACGGCACCGGCCCAUGCAAUAACGUGUCCACAGUGCAGUG UACCCACGGCAUCAAGCCCGUGGUGUCUACACAGCUGCUGCUGAAUGGCAGCCUGGCCGAGAAG GAGAUCAUCAUCAGGUCUGAGAACCUGACCAAUAACGCCAAGAUCAUCAUCGUGCACCUGAAUA ACCCAGUGAAGAUCAUCUGCACAAGGCCCGGCAAUAACACCGUGAAGAGCAUGAGAAUCGGCCC UGGCCAGACAUUCUACUAUACCGGCGACAUCAUCGGCGAUAUCAGGAGAGCCUACUGUAACAUC UCUGAGAAGACAUGGUAUGACACCCUGAAGAAUGUGAGCGAUAAGUUCCAGGAGCACUUUCCU AACGCCUCCAUCGAGUUCAAGCCAUCUGCCGGCGGCGACCUGGAGAUCACCACACACUCCUUUA AUUGCAGGGGCGAGUUCUUUUACUGUGAUACAAGCGAGCUGUUCAAUGGCACAUACAAUAACU CCACCUAUAACAGCUCCAAUAACAUCACCCUGCAGUGCAAGAUCAAGCAGAUCAUCAACAUGUGG CAGGGCGUGGGCAGAGCCAUGUAUGCCCCUCCCAUCGCCGGCAAUAUCACCUGUGAGAGCAACA UCACAGGCCUGCUGCUGACCCGGGACGGCGGAAAUAACAAGUCCACACCAGAGACAUUCAGGCC CGGCGGCGGCGACAUGAGGGAUAACUGGAGAAGCGAGCUGUACAAGUAUAAGGUGGUGGAGA UCAAGCCUCUGGGCAUCGCCCCAACAAAGUGCAAGAGGAGGGUGGUGGGCUCCCACUCUGGCAG CGGCGGCUCCGGCUCUGGCGGCCACGCAGCCGUGGGCAUGGGCGCCGUGUCUCUGGGCUUCCU GGGAGCAGCAGGCAGCACCAUGGGAGCAGCAUCCCUGACACUGACCGUGCAGGCAAGGCAGCUG CUGAGCGGCAUCGUGCAGCAGCAGAAUAACCUGCUGAGAGCCCCCGAGCCUCAGCAGCACAUGC UGCAGGACACACACUGGGGCAUCAAGCAGCUGCAGGCCCGGGUGCUGGCAAUCGAGCACUACCU GACAGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGCUGAUCUGCUGUACCAAUGU GCCCUGGAAUAACAGCUGGUCCAACAAGUCCUAUGAGGAUAUCUGGGGCCGGAAUAUGACCUG GAUGAACUGGAGCAGGGAGAUCAACAACUACACAAACACCAUCUAUCGCCUGCUGGAAAAGUCA CAGAAUCAGCAGGAGAAGAAUAAUAAGUCACUGCUGGAACUGGACUGAUAA (SEQ ID NO: 194) CE1176_FJ444437_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSVGNLWVTVYYGVPVWKEAKTTLFCASDAKAYEKEVHNVWATHACVPTDP NPQEMVLENVTENFNMWKNDMVDQMHEDVISLWDQSLKPCVKLTPLCVTLTCTNTTVSNGSSNSNAN FEEMKNCSFNATTEIKDKKKNEYALFYKLDIVPLNNSSGKYRLINCNTSAIAQACPKVTFEPIPIHYCAPAGYA ILKCNNKTFNGTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEKEIIIRSENLTNNAKTIIIHLNESVGIVCTRP SNNTVKSIRIGPGQTFYYTGDIIGDIRQAHCNVSKQNWNRTLQQVGRKLAEHFPNRNITFAHSSGGDLEIT THSFNCRGEFFYCNTSGLFNGTYHPNGTYNETAVNSSDTITLQCRIKQIINMWQEVGRAMYAPPIAGNITC NSTITGLLLTRDGGINQTGEEIFRPGGGDMRDNWRNELYKYKVVEIKPLGIAPTKCKRRVVGSHSGSGGSG SGGHAAVGIGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHMLQDTHWGIK QLQARVLAIEHYLKDQQLLGIWGCSGKLICCTNVPWNSSWSNRSQEDIWNNMTWMNWSREIDNYTHT IYSLLEESQIQQEKNNKSLLALD** (SEQ ID NO: 198) atggattggacttggattctgtttctggtcgccgccgctactcgcgtgcattcagtgggcaacctgtgggtcaccgtctactatggggtg cccgtgtggaaggaggccaagaccacactgttctgcgcctccgacgccaaggcctacgagaaggaggtgcacaacgtgtgggcca cacacgcctgcgtgcctaccgatccaaatccccaggagatggtgctggagaacgtgacagagaactttaatatgtggaagaacgac atggtggatcagatgcacgaggacgtgatctctctgtgggatcagagcctgaagccttgcgtgaagctgaccccactgtgcgtgacc ctgacatgtaccaataccacagtgtccaacggcagctccaactctaatgccaacttcgaggagatgaagaattgttcttttaacgcca ccacagagatcaaggacaagaagaagaacgagtacgccctgttctataagctggatatcgtgcccctgaacaattctagcggcaag tataggctgatcaattgcaacacaagcgccatcgcccaggcctgtccaaaggtgaccttcgagcctatcccaatccactactgcgccc ccgccggctatgccatcctgaagtgtaacaacaagaccttcaacggcaccggcccttgcaacaacgtgagcacagtgcagtgtaccc acggcatcaagccagtggtgagcacccagctgctgctgaacggctccctggcagagaaggagatcatcatccggagcgagaatctg acaaacaatgccaagaccatcatcatccacctgaacgagtccgtgggcatcgtgtgcacacggcccagcaacaataccgtgaagtc catccgcatcggccctggccagaccttctactataccggcgacatcatcggcgatatccgccaggcccactgtaatgtgagcaagca gaattggaacaggacactgcagcaagtgggcagaaagctggccgagcacttcccaaataggaacatcacctttgcccactcctctg gcggcgacctggagatcaccacacactccttcaactgcagaggcgagttcttttactgtaatacatctggcctgtttaacggcacctac caccccaatggcacatataacgagacagccgtgaatagctccgatacaatcaccctgcagtgcaggatcaagcagatcatcaacat gtggcaggaagtgggcagagccatgtatgcccctcccatcgccggcaatatcacctgtaacagcacaatcaccggcctgctgctgac acgggacggcggcatcaaccagaccggagaggagatcttccgccccggcggcggcgacatgcgggataattggcgcaacgagctg tacaagtataaggtggtggagatcaagccactgggcatcgcccccacaaagtgcaagaggagagtggtgggctcccactctggcag cggcggctccggctctggcggccacgcagccgtgggcatcggagccgtgtccctgggctttctgggagcagcaggctctaccatggg agcagccagcatcacactgaccgtgcaggcaaggcagctgctgtccggcatcgtgcagcagcagtctaacctgctgagagcccccg agcctcagcagcacatgctgcaggacacccactggggcatcaagcagctgcaggccagggtgctggccatcgagcactacctgaag gatcagcagctgctgggcatctggggctgttctggcaagctgatctgctgtacaaatgtgccatggaactctagctggagcaaccggt cccaggaggacatctggaacaatatgacctggatgaattggagcagggagatcgataactacacacacaccatctatagcctgctg gaggagtcacagattcagcaggagaaaaataataagtcactgctggcactggactgataa (SEQ ID NO: 196) AUGGAUUGGACUUGGAUUCUGUUUCUGGUCGCCGCCGCUACUCGCGUGCAUUCAGUGGGCAA CCUGUGGGUCACCGUCUACUAUGGGGUGCCCGUGUGGAAGGAGGCCAAGACCACACUGUUCUG CGCCUCCGACGCCAAGGCCUACGAGAAGGAGGUGCACAACGUGUGGGCCACACACGCCUGCGUG CCUACCGAUCCAAAUCCCCAGGAGAUGGUGCUGGAGAACGUGACAGAGAACUUUAAUAUGUGG AAGAACGACAUGGUGGAUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGAUCAGAGCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACCCUGACAUGUACCAAUACCACAGUGUCCAACG GCAGCUCCAACUCUAAUGCCAACUUCGAGGAGAUGAAGAAUUGUUCUUUUAACGCCACCACAGA GAUCAAGGACAAGAAGAAGAACGAGUACGCCCUGUUCUAUAAGCUGGAUAUCGUGCCCCUGAAC AAUUCUAGCGGCAAGUAUAGGCUGAUCAAUUGCAACACAAGCGCCAUCGCCCAGGCCUGUCCAA AGGUGACCUUCGAGCCUAUCCCAAUCCACUACUGCGCCCCCGCCGGCUAUGCCAUCCUGAAGUG UAACAACAAGACCUUCAACGGCACCGGCCCUUGCAACAACGUGAGCACAGUGCAGUGUACCCACG GCAUCAAGCCAGUGGUGAGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAGAGAAGGAGAUCAU CAUCCGGAGCGAGAAUCUGACAAACAAUGCCAAGACCAUCAUCAUCCACCUGAACGAGUCCGUG GGCAUCGUGUGCACACGGCCCAGCAACAAUACCGUGAAGUCCAUCCGCAUCGGCCCUGGCCAGA CCUUCUACUAUACCGGCGACAUCAUCGGCGAUAUCCGCCAGGCCCACUGUAAUGUGAGCAAGCA GAAUUGGAACAGGACACUGCAGCAAGUGGGCAGAAAGCUGGCCGAGCACUUCCCAAAUAGGAAC AUCACCUUUGCCCACUCCUCUGGCGGCGACCUGGAGAUCACCACACACUCCUUCAACUGCAGAG GCGAGUUCUUUUACUGUAAUACAUCUGGCCUGUUUAACGGCACCUACCACCCCAAUGGCACAUA UAACGAGACAGCCGUGAAUAGCUCCGAUACAAUCACCCUGCAGUGCAGGAUCAAGCAGAUCAUC AACAUGUGGCAGGAAGUGGGCAGAGCCAUGUAUGCCCCUCCCAUCGCCGGCAAUAUCACCUGUA ACAGCACAAUCACCGGCCUGCUGCUGACACGGGACGGCGGCAUCAACCAGACCGGAGAGGAGAU CUUCCGCCCCGGCGGCGGCGACAUGCGGGAUAAUUGGCGCAACGAGCUGUACAAGUAUAAGGU GGUGGAGAUCAAGCCACUGGGCAUCGCCCCCACAAAGUGCAAGAGGAGAGUGGUGGGCUCCCAC UCUGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCAGCCGUGGGCAUCGGAGCCGUGUCCCUG GGCUUUCUGGGAGCAGCAGGCUCUACCAUGGGAGCAGCCAGCAUCACACUGACCGUGCAGGCAA GGCAGCUGCUGUCCGGCAUCGUGCAGCAGCAGUCUAACCUGCUGAGAGCCCCCGAGCCUCAGCA GCACAUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCCAUCGAG CACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUCUGGCAAGCUGAUCUGCUGU ACAAAUGUGCCAUGGAACUCUAGCUGGAGCAACCGGUCCCAGGAGGACAUCUGGAACAAUAUGA CCUGGAUGAAUUGGAGCAGGGAGAUCGAUAACUACACACACACCAUCUAUAGCCUGCUGGAGGA GUCACAGAUUCAGCAGGAGAAAAAUAAUAAGUCACUGCUGGCACUGGACUGAUAA (SEQ ID NO: 197) 25710_EF117271_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSGGNLWVTVYYGVPVWKEATTTLFCASDAKAYDKEVHNVWATHACVPTDP NPQEMVLGNVTENFNMWKNEMVNQMHEDVISLWDQSLKPCVKLTPLCVTLECSNVTYNESMKEVKN CSFNLTTELRDKKQKVHALFYRLDIVPLNDTEKKNSSRPYRLINCNTSAITQACPKVTFDPIPIHYCTPAGYAIL KCNDKKFNGTGPCHKVSTVQCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLTNNAKTIIVHLNQSVEIVCARP SNNTVTSIRIGPGQTFYYTGAITGDIRQAHCNISKDKWNETLQRVGEKLAEHFPNKTIKFASSSGGDLEITTH SFNCRGEFFYCNTSGLFNGTFNGTYVSPNSTDSNSSSIITIPCRIKQIINMWQEVGRAMYAPPIAGNITCKS NITGLLLVRDGGTGSESNKTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTKCKRRVVGSHSGSGGS GSGGHAAVGIGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIK QLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNYSWSNRSQDDIWDNMTWMNWSKEISNYTNTI YKLLEDSQIQQEKNNKSLLALD** (SEQ ID NO: 201) atggactggacttggattctgttcctggtcgccgccgctactcgcgtgcattctgggggcaacctgtgggtcaccgtgtattatggagtg cccgtgtggaaggaggccaccacaaccctgttctgcgccagcgacgccaaggcctacgataaggaggtgcacaacgtgtgggcaa cccacgcatgcgtgccaacagacccaaacccccaggagatggtgctgggcaatgtgaccgagaactttaatatgtggaagaacgag atggtgaatcagatgcacgaggacgtgatctccctgtgggatcagtctctgaagccttgcgtgaagctgaccccactgtgcgtgacac tggagtgttccaacgtgacctataatgagtctatgaaggaggtgaagaactgttccttcaatctgacaaccgagctgagggataaga agcagaaggtgcacgccctgttttacagactggacatcgtgcccctgaacgataccgagaagaagaatagctcccggccttatcgcc tgatcaactgcaatacaagcgccatcacccaggcctgtcctaaggtgaccttcgaccctatcccaatccactactgcacaccagccgg ctatgccatcctgaagtgtaacgataagaagtttaatggcaccggcccatgccacaaggtgtccacagtgcagtgtacccacggcat caagcccgtggtgtctacacagctgctgctgaacggcagcctggcagagggcgagatcatcatcaggagcgagaacctgaccaaca atgccaagacaatcatcgtgcacctgaatcagtccgtggagatcgtgtgcgcccggccaagcaacaatacagtgacctccatcagga tcggaccaggacagacattctactataccggcgccatcacaggcgacatcaggcaggcccactgtaacatcagcaaggataagtgg aatgagacactgcagagagtgggcgagaagctggccgagcacttccccaacaagacaatcaagtttgcctctagctccggcggcga cctggagatcacaacccactcctttaactgcaggggcgagttcttttactgtaatacctctggcctgttcaacggcacctttaatggcac atacgtgagccccaacagcaccgattccaattctagctccatcatcacaatcccttgccggatcaagcagatcatcaatatgtggcag gaagtgggaagggcaatgtacgcccctcccatcgccggcaacatcacctgtaagtccaatatcacaggcctgctgctggtgagggac ggcggaaccggctctgagagcaacaagacagagatcttcagacccggcggcggcgacatgagggataattggagatctgagctgt acaagtataaggtggtggagatcaagccactgggcgtggcccccaccaagtgcaagaggagagtggtgggctcccactctggcagc ggcggctccggctctggcggccacgcagccgtgggcatcggagccgtgtccctgggctttctgggagcagcaggctctacaatggga gcagccagcatcacactgaccgtgcaggcaaggcagctgctgagcggcatcgtgcagcagcagtccaacctgctgagggcaccag agcctcagcagcacctgctgcaggacacccactggggcatcaagcagctgcagacacgggtgctggccatcgagcactacctgaag gatcagcagctgctgggcatctggggctgttctggcaagctgatctgctgtaccgccgtgccctggaactatagctggtccaatcgca gccaggacgatatctgggacaacatgacatggatgaattggtctaaggagatcagcaactacacaaataccatctataagctgctgg aagatagtcagattcagcaggaaaagaacaataagtcactgctggcactggattgataa (SEQ ID NO: 199) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGCCGCUACUCGCGUGCAUUCUGGGGGCAAC CUGUGGGUCACCGUGUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCAGCGACGCCAAGGCCUACGAUAAGGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUGC CAACAGACCCAAACCCCCAGGAGAUGGUGCUGGGCAAUGUGACCGAGAACUUUAAUAUGUGGAA GAACGAGAUGGUGAAUCAGAUGCACGAGGACGUGAUCUCCCUGUGGGAUCAGUCUCUGAAGCC UUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUUCCAACGUGACCUAUAAUGAGUC UAUGAAGGAGGUGAAGAACUGUUCCUUCAAUCUGACAACCGAGCUGAGGGAUAAGAAGCAGAA GGUGCACGCCCUGUUUUACAGACUGGACAUCGUGCCCCUGAACGAUACCGAGAAGAAGAAUAGC UCCCGGCCUUAUCGCCUGAUCAACUGCAAUACAAGCGCCAUCACCCAGGCCUGUCCUAAGGUGA CCUUCGACCCUAUCCCAAUCCACUACUGCACACCAGCCGGCUAUGCCAUCCUGAAGUGUAACGAU AAGAAGUUUAAUGGCACCGGCCCAUGCCACAAGGUGUCCACAGUGCAGUGUACCCACGGCAUCA AGCCCGUGGUGUCUACACAGCUGCUGCUGAACGGCAGCCUGGCAGAGGGCGAGAUCAUCAUCA GGAGCGAGAACCUGACCAACAAUGCCAAGACAAUCAUCGUGCACCUGAAUCAGUCCGUGGAGAU CGUGUGCGCCCGGCCAAGCAACAAUACAGUGACCUCCAUCAGGAUCGGACCAGGACAGACAUUC UACUAUACCGGCGCCAUCACAGGCGACAUCAGGCAGGCCCACUGUAACAUCAGCAAGGAUAAGU GGAAUGAGACACUGCAGAGAGUGGGCGAGAAGCUGGCCGAGCACUUCCCCAACAAGACAAUCAA GUUUGCCUCUAGCUCCGGCGGCGACCUGGAGAUCACAACCCACUCCUUUAACUGCAGGGGCGAG UUCUUUUACUGUAAUACCUCUGGCCUGUUCAACGGCACCUUUAAUGGCACAUACGUGAGCCCC AACAGCACCGAUUCCAAUUCUAGCUCCAUCAUCACAAUCCCUUGCCGGAUCAAGCAGAUCAUCAA UAUGUGGCAGGAAGUGGGAAGGGCAAUGUACGCCCCUCCCAUCGCCGGCAACAUCACCUGUAAG UCCAAUAUCACAGGCCUGCUGCUGGUGAGGGACGGCGGAACCGGCUCUGAGAGCAACAAGACAG AGAUCUUCAGACCCGGCGGCGGCGACAUGAGGGAUAAUUGGAGAUCUGAGCUGUACAAGUAUA AGGUGGUGGAGAUCAAGCCACUGGGCGUGGCCCCCACCAAGUGCAAGAGGAGAGUGGUGGGCU CCCACUCUGGCAGCGGCGGCUCCGGCUCUGGCGGCCACGCAGCCGUGGGCAUCGGAGCCGUGUC CCUGGGCUUUCUGGGAGCAGCAGGCUCUACAAUGGGAGCAGCCAGCAUCACACUGACCGUGCAG GCAAGGCAGCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGGGCACCAGAGCCUC AGCAGCACCUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUGCAGACACGGGUGCUGGCCAU CGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUCUGGCAAGCUGAUCUG CUGUACCGCCGUGCCCUGGAACUAUAGCUGGUCCAAUCGCAGCCAGGACGAUAUCUGGGACAAC AUGACAUGGAUGAAUUGGUCUAAGGAGAUCAGCAACUACACAAAUACCAUCUAUAAGCUGCUG GAAGAUAGUCAGAUUCAGCAGGAAAAGAACAAUAAGUCACUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 200) BJOX2000_HM215364_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSVGNLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDP DPQEMFLENVTENFNMWKNNMVDQMHEDVISLWDQSLKPCVKLTPLCVTLECKNVNSSSSDTKNGTD PEMKNCSFNATTELRDRKQKVYALFYKLDIVPLNEKNSSEYRLINCNTSTITQACPKVTFDPIPIHYCTPAGYA ILKCNDEKFNGTGPCSNVSTVQCTHGIKPVVSTQLLLNGSLAEKGIIIRSENLTNNVKTIIVHLNQSVEILCIRP NNNTVKSIRIGPGQTFYYTGEIIGDIRQAHCNISGKVWNETLQRVGEKLAEYFPNKTIKFASSSGGDLEITTH SFNCGGEFFYCNTSKLFNGTFNGTYMPNVTEGNSTISIPCRIKQIINMWQKVGRAMYAPPIEGNITCKSKIT GLLLERDGGPENDTEIFRPGGGDMRNNWRSELYKYKVVEIKPLGVAPTECKRRVVGSHSGSGGSGSGGH AAVGIGAVSLGFLGVAGSTMGAASMALTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIKQLQT RVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQEEIWENMTWMNWSKEISNYTDTIYRLLE DSQNQQERNNKSLLALD** (SEQ ID NO: 204) atggactggacttggattctgtttctggtcgcagcagcaactcgggtgcatagcgtcggcaacctgtgggtcactgtctactacggggt gcccgtgtggaaggaggccaccacaaccctgttctgcgccagcgacgccaaggcctacgataccgaggtgcacaacgtgtgggcaa cccacgcatgcgtgcctacagacccagatccccaggagatgttcctggagaacgtgacagagaacttcaacatgtggaagaacaat atggtggaccagatgcacgaggatgtgatcagcctgtgggaccagtccctgaagccttgcgtgaagctgaccccactgtgcgtgaca ctggagtgtaagaatgtgaacagctcctctagcgacaccaagaacggcacagatcctgagatgaagaattgttctttcaacgccaca accgagctgcgggaccgcaagcagaaggtgtacgccctgttttataagctggatatcgtgccactgaatgagaagaactcctctgag tatcggctgatcaattgcaacacaagcaccatcacacaggcctgtcccaaggtgaccttcgaccctatcccaatccactactgcacac ctgccggctatgccatcctgaagtgtaatgatgagaagtttaacggcaccggcccatgctccaacgtgagcaccgtgcagtgtacac acggcatcaagcccgtggtgagcacacagctgctgctgaacggctccctggccgagaagggcatcatcatccgctccgagaatctg accaacaatgtgaagacaatcatcgtgcacctgaaccagtccgtggagatcctgtgcatccggccaaacaataacaccgtgaagtct atccgcatcggccccggccagaccttctactatacaggcgagatcatcggcgacatccggcaggcccactgtaatatctctggcaag gtctggaacgagacactgcagagggtgggagagaagctggcagagtacttcccaaacaagacaatcaagtttgccagctcctctgg cggcgatctggagatcacaacccactcttttaattgcggcggcgagttcttttactgtaacaccagcaagctgttcaatggcaccttta acggcacatatatgcctaatgtgaccgagggcaacagcacaatctccatcccatgccggatcaagcagatcatcaatatgtggcaga aagtgggccgcgccatgtatgcccctcccatcgagggcaacatcacctgtaagagcaagatcacaggcctgctgctggagagggac ggcggaccagagaacgataccgagatcttcagacccggcggcggcgacatgaggaataactggagatccgagctgtacaagtata aggtggtggagatcaagccactgggagtggcaccaaccgagtgcaagaggagagtggtgggctctcacagcggctccggcggctct ggcagcggcggccacgccgccgtgggcatcggagccgtgagcctgggctttctgggagtggcaggctctaccatgggagcagcaag catggcactgacagtgcaggccaggcagctgctgtccggcatcgtgcagcagcagtctaatctgctgagagcaccagagcctcagc agcacctgctgcaggacacccactggggcatcaagcagctgcagacaagggtgctggccatcgagcactacctgaaggatcagca gctgctgggcatctggggctgttccggcaagctgatctgctgtaccgccgtgccttggaatagctcctggtctaacaagagccaggag gagatctgggagaatatgacatggatgaactggtccaaggagatctctaactacaccgatacaatctatagactgctggaagatagt cagaatcagcaggagagaaataataagtcactgctggcactggattgataa (SEQ ID NO: 202) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGCAGCAACUCGGGUGCAUAGCGUCGGCAAC CUGUGGGUCACUGUCUACUACGGGGUGCCCGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCAGCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUGC CUACAGACCCAGAUCCCCAGGAGAUGUUCCUGGAGAACGUGACAGAGAACUUCAACAUGUGGAA GAACAAUAUGGUGGACCAGAUGCACGAGGAUGUGAUCAGCCUGUGGGACCAGUCCCUGAAGCC UUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUAAGAAUGUGAACAGCUCCUCUAG CGACACCAAGAACGGCACAGAUCCUGAGAUGAAGAAUUGUUCUUUCAACGCCACAACCGAGCUG CGGGACCGCAAGCAGAAGGUGUACGCCCUGUUUUAUAAGCUGGAUAUCGUGCCACUGAAUGAG AAGAACUCCUCUGAGUAUCGGCUGAUCAAUUGCAACACAAGCACCAUCACACAGGCCUGUCCCAA GGUGACCUUCGACCCUAUCCCAAUCCACUACUGCACACCUGCCGGCUAUGCCAUCCUGAAGUGU AAUGAUGAGAAGUUUAACGGCACCGGCCCAUGCUCCAACGUGAGCACCGUGCAGUGUACACACG GCAUCAAGCCCGUGGUGAGCACACAGCUGCUGCUGAACGGCUCCCUGGCCGAGAAGGGCAUCAU CAUCCGCUCCGAGAAUCUGACCAACAAUGUGAAGACAAUCAUCGUGCACCUGAACCAGUCCGUG GAGAUCCUGUGCAUCCGGCCAAACAAUAACACCGUGAAGUCUAUCCGCAUCGGCCCCGGCCAGA CCUUCUACUAUACAGGCGAGAUCAUCGGCGACAUCCGGCAGGCCCACUGUAAUAUCUCUGGCAA GGUCUGGAACGAGACACUGCAGAGGGUGGGAGAGAAGCUGGCAGAGUACUUCCCAAACAAGAC AAUCAAGUUUGCCAGCUCCUCUGGCGGCGAUCUGGAGAUCACAACCCACUCUUUUAAUUGCGG CGGCGAGUUCUUUUACUGUAACACCAGCAAGCUGUUCAAUGGCACCUUUAACGGCACAUAUAU GCCUAAUGUGACCGAGGGCAACAGCACAAUCUCCAUCCCAUGCCGGAUCAAGCAGAUCAUCAAU AUGUGGCAGAAAGUGGGCCGCGCCAUGUAUGCCCCUCCCAUCGAGGGCAACAUCACCUGUAAGA GCAAGAUCACAGGCCUGCUGCUGGAGAGGGACGGCGGACCAGAGAACGAUACCGAGAUCUUCAG ACCCGGCGGCGGCGACAUGAGGAAUAACUGGAGAUCCGAGCUGUACAAGUAUAAGGUGGUGGA GAUCAAGCCACUGGGAGUGGCACCAACCGAGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGG CUCCGGCGGCUCUGGCAGCGGCGGCCACGCCGCCGUGGGCAUCGGAGCCGUGAGCCUGGGCUU UCUGGGAGUGGCAGGCUCUACCAUGGGAGCAGCAAGCAUGGCACUGACAGUGCAGGCCAGGCA GCUGCUGUCCGGCAUCGUGCAGCAGCAGUCUAAUCUGCUGAGAGCACCAGAGCCUCAGCAGCAC CUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUGCAGACAAGGGUGCUGGCCAUCGAGCACU ACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGCUGUUCCGGCAAGCUGAUCUGCUGUACCG CCGUGCCUUGGAAUAGCUCCUGGUCUAACAAGAGCCAGGAGGAGAUCUGGGAGAAUAUGACAU GGAUGAACUGGUCCAAGGAGAUCUCUAACUACACCGAUACAAUCUAUAGACUGCUGGAAGAUA GUCAGAAUCAGCAGGAGAGAAAUAAUAAGUCACUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 203) CH119_EF117261_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSVGNLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHACVPTDP SPQELVLENVTENFNMWKNEMVNQMHEDVISLWDQSLKPCVKLTPLCVTLECSKVSNNETDKYNGTEE MKNCSFNATTVVRDRQQKVYALFYRLDIVPLTEKNSSENSSKYYRLINCNTSAITQACPKVSFEPIPIHYCTPA GYAILKCNDKTFNGTGPCHNVSTVQCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLTNNVKTILVHLNQSVEI VCTRPNNNTVKSIRIGPGQTFYYTGDIIGDIRQAHCNISKWHETLKRVSEKLAEHFPNKTINFTSSSGGDLEIT THSFTCRGEFFYCNTSGLFNSTYMPNGTYLHGDTNSNSSITIPCRIKQIINMWQEVGRAMYAPPIEGNITCK SNITGLLLVRDGGTESNNTETNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTACKRRVVGSHSG SGGSGSGGHAAVGIGAVSLGFLGVAGSTMGAASMTLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDT HWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSQKEIWDNMTWMNWSKEIS NYTNTIYKLLEDSQNQQESNNKSLLALD** (SEQ ID NO: 207) atggactggacttggattctgtttctggtcgcagccgcaactcgcgtgcattccgtgggcaacctgtgggtcaccgtctactatggggt gccagtgtggaaggaggccaccacaaccctgttctgcgcctccgacgccaaggcctacgataccgaggtgcacaacgtgtgggcaa cacacgcatgcgtgccaaccgacccatctccccaggagctggtgctggagaatgtgacagagaacttcaacatgtggaagaatgag atggtgaaccagatgcacgaggacgtgatctccctgtgggatcagtctctgaagccttgcgtgaagctgacaccactgtgcgtgaccc tggagtgttccaaggtgtctaacaatgagacagacaagtataacggcaccgaggagatgaagaattgtagcttcaacgcaacaacc gtggtgcgggaccgccagcagaaggtgtacgccctgttttataggctggatatcgtgcccctgaccgagaagaatagctccgagaac tctagcaagtactatagactgatcaattgcaacacatctgccatcacccaggcctgtccaaaggtgagcttcgagcctatcccaatcc actactgcacccccgccggctatgccatcctgaagtgtaatgacaagaccttcaacggcaccggcccttgccacaacgtgagcacag tgcagtgtacccacggcatcaagccagtggtgagcacacagctgctgctgaatggctccctggccgagggcgagatcatcatccggt ccgagaacctgacaaacaatgtgaagaccatcctggtgcacctgaatcagagcgtggagatcgtgtgcacacggcccaacaataac accgtgaagtccatccgcatcggccctggccagacattctactataccggcgacatcatcggcgatatccggcaggcccactgtaac atctccaagtggcacgagacactgaagcgcgtgtctgagaagctggccgagcacttccctaataagacaatcaactttacctcctcta gcggcggcgacctggagatcacaacccactctttcacctgccgcggcgagttcttttactgtaatacaagcggcctgtttaactccaca tacatgcccaatggcacctatctgcacggcgatacaaattccaactcctctatcaccatcccttgcaggatcaagcagatcatcaaca tgtggcaggaagtgggcagagccatgtatgcccctcccatcgagggcaacatcacctgtaagtctaatatcacaggcctgctgctggt gcgggacggcggaaccgagagcaataacacagagacaaataacacagagatcttccgccccggcggcggcgacatgagggataa ctggagaagcgagctgtacaagtataaggtggtggagatcaagccactgggagtggcaccaaccgcatgcaagaggagagtggtg ggctctcacagcggctccggcggctctggcagcggcggccacgccgccgtgggcatcggagccgtgtccctgggctttctgggagtg gcaggctctaccatgggagcagccagcatgacactgaccgtgcaggcaaggcagctgctgtccggcatcgtgcagcagcagtctaa cctgctgagagcaccagagcctcagcagcacctgctgcaggacacccactggggcatcaagcagctgcagacacgggtgctggcc atcgagcactacctgaaggatcagcagctgctgggcatctggggctgtagcggcaagctgatctgctgtaccgccgtgccttggaat agctcctggagcaacaagtcccagaaggagatctgggataatatgacatggatgaactggtctaaggagatcagcaattacacaaa caccatctataagctgctggaggactcacagaatcagcaggaatcaaacaacaaatccctgctggcactggactgataa (SEQ ID NO: 205) AUGGACUGGACUUGGAUUCUGUUUCUGGUCGCAGCCGCAACUCGCGUGCAUUCCGUGGGCAAC CUGUGGGUCACCGUCUACUAUGGGGUGCCAGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCUCCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCAACACACGCAUGCGUGC CAACCGACCCAUCUCCCCAGGAGCUGGUGCUGGAGAAUGUGACAGAGAACUUCAACAUGUGGAA GAAUGAGAUGGUGAACCAGAUGCACGAGGACGUGAUCUCCCUGUGGGAUCAGUCUCUGAAGCC UUGCGUGAAGCUGACACCACUGUGCGUGACCCUGGAGUGUUCCAAGGUGUCUAACAAUGAGAC AGACAAGUAUAACGGCACCGAGGAGAUGAAGAAUUGUAGCUUCAACGCAACAACCGUGGUGCG GGACCGCCAGCAGAAGGUGUACGCCCUGUUUUAUAGGCUGGAUAUCGUGCCCCUGACCGAGAA GAAUAGCUCCGAGAACUCUAGCAAGUACUAUAGACUGAUCAAUUGCAACACAUCUGCCAUCACC CAGGCCUGUCCAAAGGUGAGCUUCGAGCCUAUCCCAAUCCACUACUGCACCCCCGCCGGCUAUG CCAUCCUGAAGUGUAAUGACAAGACCUUCAACGGCACCGGCCCUUGCCACAACGUGAGCACAGU GCAGUGUACCCACGGCAUCAAGCCAGUGGUGAGCACACAGCUGCUGCUGAAUGGCUCCCUGGCC GAGGGCGAGAUCAUCAUCCGGUCCGAGAACCUGACAAACAAUGUGAAGACCAUCCUGGUGCACC UGAAUCAGAGCGUGGAGAUCGUGUGCACACGGCCCAACAAUAACACCGUGAAGUCCAUCCGCAU CGGCCCUGGCCAGACAUUCUACUAUACCGGCGACAUCAUCGGCGAUAUCCGGCAGGCCCACUGU AACAUCUCCAAGUGGCACGAGACACUGAAGCGCGUGUCUGAGAAGCUGGCCGAGCACUUCCCUA AUAAGACAAUCAACUUUACCUCCUCUAGCGGCGGCGACCUGGAGAUCACAACCCACUCUUUCAC CUGCCGCGGCGAGUUCUUUUACUGUAAUACAAGCGGCCUGUUUAACUCCACAUACAUGCCCAAU GGCACCUAUCUGCACGGCGAUACAAAUUCCAACUCCUCUAUCACCAUCCCUUGCAGGAUCAAGC AGAUCAUCAACAUGUGGCAGGAAGUGGGCAGAGCCAUGUAUGCCCCUCCCAUCGAGGGCAACAU CACCUGUAAGUCUAAUAUCACAGGCCUGCUGCUGGUGCGGGACGGCGGAACCGAGAGCAAUAAC ACAGAGACAAAUAACACAGAGAUCUUCCGCCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAA GCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGAGUGGCACCAACCGCAUGCA AGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCCACGCCGCCG UGGGCAUCGGAGCCGUGUCCCUGGGCUUUCUGGGAGUGGCAGGCUCUACCAUGGGAGCAGCCA GCAUGACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGGCAUCGUGCAGCAGCAGUCUAACCU GCUGAGAGCACCAGAGCCUCAGCAGCACCUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUG CAGACACGGGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGC UGUAGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCUUGGAAUAGCUCCUGGAGCAACAAGUCC CAGAAGGAGAUCUGGGAUAAUAUGACAUGGAUGAACUGGUCUAAGGAGAUCAGCAAUUACACA AACACCAUCUAUAAGCUGCUGGAGGACUCACAGAAUCAGCAGGAAUCAAACAACAAAUCCCUGCU GGCACUGGACUGAUAA (SEQ ID NO: 206) X1632_FJ817370_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSSNNLWVTVYYGVPVWEDADTTLFCASDAKAYSTESHNVWATHACVPTDP NPQEIYLENVTEDFNMWENNMVEQMQEDIISLWDESLKPCVKLTPLCVTLTCTNVTNVTDSVGTNSRLK GYKEELKNCSFNTTTEIRDKKKQEYALFYKLDIVPINDNSNNSNGYRLINCNVSTIKQACPKVSFDPIPIHYCA PAGFAILKCRDKEFNGTGTCRNVSTVQCTHGIKPVVSTQLLLNGSLAEGDIIIRSENITDNAKTIIVHLNKTVSI TCTRPNNNTVKSIRIGPGQALYYTGAIIGDTRQAHCNINGSEWYEMIQNVKNKLNETFKKNITFAPSSGGD LEITTHSFNCRGEFFYCNTSELFNSSHLFNGSTLSTNGTITLPCRIKQIVRMWQRVGQAMYAPPIAGNITCR SNITGLLLTRDGGTNKDTNEAETFRPGGGDMRDNWRSELYKYKVVKIKPLGVAPTRCRRRVVGSHSGSGG SGSGGHAAIGLGTVSLGFLGTAGSTMGAASITLTVQVRQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIK QLQARVLAVEHYLKDQQJLGIWGCSGKLICCTNVPWNSSWSNKSYSDIWDNLTWINWSREISNYTQQIYT LLEESQNQQEKNNQSLLALD** (SEQ ID NO: 210) atggactggacttggattctgttcctggtcgccgccgctacacgggtgcattcatcaaataacctgtgggtcactgtctactatggggtg cccgtgtgggaggacgccgataccacactgttctgcgcatccgacgcaaaggcatactccaccgagtctcacaacgtgtgggcaacc cacgcatgcgtgccaacagacccaaacccccaggagatctatctggagaacgtgacagaggacttcaacatgtgggagaacaatat ggtggagcagatgcaggaggacatcatcagcctgtgggatgagtccctgaagccttgcgtgaagctgaccccactgtgcgtgacact gacctgtacaaatgtgaccaacgtgacagactctgtgggcacaaatagccgcctgaagggctacaaggaggagctgaagaactgta gcttcaataccacaaccgagatcagggataagaagaagcaggagtacgccctgttttataagctggacatcgtgccaatcaatgata acagcaacaattccaacggctacagactgatcaattgcaacgtgtccaccatcaagcaggcctgtccaaaggtgtctttcgaccctat cccaatccactattgcgcaccagcaggattcgcaatcctgaagtgtcgcgataaggagtttaatggcaccggcacatgcaggaacgt gagcaccgtgcagtgtacacacggcatcaagcccgtggtgtctacccagctgctgctgaatggcagcctggccgagggcgacatcat catcagatccgagaacatcaccgataatgccaagacaatcatcgtgcacctgaacaagaccgtgagcatcacctgcacacgcccca acaataacacagtgaagtccatcaggatcggccctggccaggccctgtactataccggagcaatcatcggcgacacaaggcaggcc cactgtaatatcaacggctccgagtggtacgagatgatccagaatgtgaagaacaagctgaatgagacattcaagaagaacatcac atttgcccccagctccggcggcgatctggagatcacaacccactcttttaactgccgcggcgagttcttttattgtaacaccagcgagc tgttcaattctagccacctgtttaacggctctaccctgagcacaaacggcaccatcacactgccttgcaggatcaagcagatcgtgcg catgtggcagagggtgggacaggcaatgtacgcccctcccatcgccggcaatatcacctgtagatctaacatcaccggcctgctgct gacacgggacggcggaaccaacaaggatacaaatgaggcagagacattcagacccggcggcggcgacatgagagataactggcg gagcgagctgtacaagtataaggtggtgaagatcaagccactgggagtggcaccaaccaggtgcaggagacgggtggtgggcagc cactccggctctggcggcagcggctccggcggccacgcagcaatcggcctgggcaccgtgagcctgggctttctgggaaccgcagg ctccacaatgggagcagcctctatcaccctgacagtgcaggtgagacagctgctgagcggcatcgtgcagcagcagtccaacctgct gagggcaccagagcctcagcagcacctgctgcaggacacccactggggcatcaagcagctgcaggcccgcgtgctggcagtggag cactacctgaaggatcagcagatcctgggcatctggggctgttccggcaagctgatctgctgtaccaacgtgccctggaattcctcttg gtctaataagtcttatagcgacatctgggataacctgacatggatcaattggtccagggagatctctaactacacccagcagatctat acactgctggaagaaagtcagaatcagcaggagaagaataatcagagcctgctggcactggattgataa (SEQ ID NO: 208) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGCCGCUACACGGGUGCAUUCAUCAAAUAAC CUGUGGGUCACUGUCUACUAUGGGGUGCCCGUGUGGGAGGACGCCGAUACCACACUGUUCUGC GCAUCCGACGCAAAGGCAUACUCCACCGAGUCUCACAACGUGUGGGCAACCCACGCAUGCGUGCC AACAGACCCAAACCCCCAGGAGAUCUAUCUGGAGAACGUGACAGAGGACUUCAACAUGUGGGAG AACAAUAUGGUGGAGCAGAUGCAGGAGGACAUCAUCAGCCUGUGGGAUGAGUCCCUGAAGCCU UGCGUGAAGCUGACCCCACUGUGCGUGACACUGACCUGUACAAAUGUGACCAACGUGACAGACU CUGUGGGCACAAAUAGCCGCCUGAAGGGCUACAAGGAGGAGCUGAAGAACUGUAGCUUCAAUA CCACAACCGAGAUCAGGGAUAAGAAGAAGCAGGAGUACGCCCUGUUUUAUAAGCUGGACAUCGU GCCAAUCAAUGAUAACAGCAACAAUUCCAACGGCUACAGACUGAUCAAUUGCAACGUGUCCACCA UCAAGCAGGCCUGUCCAAAGGUGUCUUUCGACCCUAUCCCAAUCCACUAUUGCGCACCAGCAGG AUUCGCAAUCCUGAAGUGUCGCGAUAAGGAGUUUAAUGGCACCGGCACAUGCAGGAACGUGAG CACCGUGCAGUGUACACACGGCAUCAAGCCCGUGGUGUCUACCCAGCUGCUGCUGAAUGGCAGC CUGGCCGAGGGCGACAUCAUCAUCAGAUCCGAGAACAUCACCGAUAAUGCCAAGACAAUCAUCG UGCACCUGAACAAGACCGUGAGCAUCACCUGCACACGCCCCAACAAUAACACAGUGAAGUCCAUC AGGAUCGGCCCUGGCCAGGCCCUGUACUAUACCGGAGCAAUCAUCGGCGACACAAGGCAGGCCC ACUGUAAUAUCAACGGCUCCGAGUGGUACGAGAUGAUCCAGAAUGUGAAGAACAAGCUGAAUG AGACAUUCAAGAAGAACAUCACAUUUGCCCCCAGCUCCGGCGGCGAUCUGGAGAUCACAACCCAC UCUUUUAACUGCCGCGGCGAGUUCUUUUAUUGUAACACCAGCGAGCUGUUCAAUUCUAGCCAC CUGUUUAACGGCUCUACCCUGAGCACAAACGGCACCAUCACACUGCCUUGCAGGAUCAAGCAGA UCGUGCGCAUGUGGCAGAGGGUGGGACAGGCAAUGUACGCCCCUCCCAUCGCCGGCAAUAUCAC CUGUAGAUCUAACAUCACCGGCCUGCUGCUGACACGGGACGGCGGAACCAACAAGGAUACAAAU GAGGCAGAGACAUUCAGACCCGGCGGCGGCGACAUGAGAGAUAACUGGCGGAGCGAGCUGUAC AAGUAUAAGGUGGUGAAGAUCAAGCCACUGGGAGUGGCACCAACCAGGUGCAGGAGACGGGUG GUGGGCAGCCACUCCGGCUCUGGCGGCAGCGGCUCCGGCGGCCACGCAGCAAUCGGCCUGGGCA CCGUGAGCCUGGGCUUUCUGGGAACCGCAGGCUCCACAAUGGGAGCAGCCUCUAUCACCCUGAC AGUGCAGGUGAGACAGCUGCUGAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGGGCACCA GAGCCUCAGCAGCACCUGCUGCAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGCGUGC UGGCAGUGGAGCACUACCUGAAGGAUCAGCAGAUCCUGGGCAUCUGGGGCUGUUCCGGCAAGC UGAUCUGCUGUACCAACGUGCCCUGGAAUUCCUCUUGGUCUAAUAAGUCUUAUAGCGACAUCU GGGAUAACCUGACAUGGAUCAAUUGGUCCAGGGAGAUCUCUAACUACACCCAGCAGAUCUAUAC ACUGCUGGAAGAAAGUCAGAAUCAGCAGGAGAAGAAUAAUCAGAGCCUGCUGGCACUGGAUUG AUAA (SEQ ID NO: 209) CNE8_HM215427_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSSDNLWVTVYYGVPVWRDADTTLFCASDAKAYDTEVHNVWATHACVPTDP NPQEIHLENVTENFNMWKNKMAEQMQEDVISLWDESLKPCVQLTPLCVTLNCTNANLNATVNASTTIG NITDEVRNCSFNTTTELRDKKQNVYALFYKLDIVPINNNSEYRLINCNTSVIKQACPKVSFDPIPIHYCAPAGY AILRCNDKNFNGTGPCKNVSSVQCTHGIKPVVSTQLLLNGSLAEDEIIIRSENLTDNVKTIIVHLNKSVEINCT RPSNNTVTSVRIGPGQVFYYTGDIIGDIRKAYCEINRTKWHETLKQVATKLREHFNKTIIFQPPSGGDIEITM HHFNCRGEFFYCNTTKLFNSTWGENTTMEGHNDTIVLPCRIKQIVNMWQGVGQAMYAPPIRGSINCVS NITGILLTRDGGTNMSNETFRPGGGNIKDNWRSELYKYKVVEIEPLGIAPTKCKRRVVGSHSGSGGSGSGG HAAVGIGAMSFGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHLLQDTHWGIKQLQA RVLAVEHYLKDQKFLGLWGCSGKIICCTAVPWNSTWSNRSYEEIWDNMTWINWSREISNYTSQIYEILTES QNQQDRNNKSLLELD** (SEQ ID NO: 213) atggactggacttggattctgttcctggtcgccgctgctacacgagtgcattcatctgataacctgtgggtcaccgtctactatggcgtg ccagtgtggcgggacgccgataccacactgttctgcgccagcgacgccaaggcctacgataccgaggtgcacaacgtgtgggcaac ccacgcatgcgtgccaacagaccctaatccacaggagatccacctggagaacgtgacagagaacttcaacatgtggaagaacaag atggccgagcagatgcaggaggacgtgatctccctgtgggatgagtctctgaagccctgcgtgcagctgacccctctgtgcgtgaca ctgaattgtaccaatgccaacctgaatgccaccgtgaatgcctccaccacaatcggcaacatcacagatgaggtgcggaactgttctt tcaataccacaaccgagctgcgcgacaagaagcagaacgtgtacgccctgttttataagctggatatcgtgcccatcaacaataact ccgagtatcggctgatcaactgcaatacctctgtgatcaagcaggcctgtcctaaggtgagcttcgaccccatccctatccactactgc gcaccagcaggatatgcaatcctgcgctgtaatgataagaactttaatggcacaggcccctgcaagaacgtgagctccgtgcagtgt acccacggcatcaagcctgtggtgtctacacagctgctgctgaacggcagcctggccgaggacgagatcatcatcaggagcgagaa cctgacagataatgtgaagaccatcatcgtgcacctgaacaagtccgtggagatcaattgcaccaggccatctaataacacagtgac cagcgtgagaatcggccccggccaggtgttctactatacaggcgacatcatcggcgatatccggaaggcctactgtgagatcaatcg cacaaagtggcacgagacactgaagcaggtggccaccaagctgagggagcacttcaacaagacaatcatctttcagcccccttccg gcggcgacatcgagatcaccatgcaccacttcaactgcagaggcgagttcttttactgtaacacaaccaagctgtttaattctacctgg ggcgagaacacaaccatggagggccacaatgatacaatcgtgctgccttgcagaatcaagcagatcgtgaacatgtggcagggagt gggacaggcaatgtatgccccacccatcaggggcagcatcaactgcgtgagcaatatcacaggcatcctgctgaccagagacggcg gaacaaacatgtctaatgagacattcaggcctggcggcggcaacatcaaggataattggagaagcgagctgtacaagtataaggtg gtggagatcgagcctctgggcatcgccccaacaaagtgcaagaggagagtggtgggctctcacagcggctccggcggctctggcag cggcggccacgccgccgtgggcatcggcgccatgagcttcggctttctgggagcagcaggctccaccatgggagcagcctctatcac actgaccgtgcaggcaaggcagctgctgagcggcatcgtgcagcagcagtccaacctgctgagggcaccagagccacagcagcac ctgctgcaggacacccactggggcatcaagcagctgcaggcccgcgtgctggcagtggagcactacctgaaggatcagaagtttct gggcctgtggggctgttccggcaagatcatctgctgtaccgccgtgccttggaactccacatggtctaatcggagctatgaggagatc tgggacaacatgacctggatcaattggtcccgcgagatctctaactacacaagccagatctatgagatcctgaccgaatcacagaat cagcaggacagaaacaacaaatcactgctggaactggactgataa (SEQ ID NO: 211) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGCUGCUACACGAGUGCAUUCAUCUGAUAAC CUGUGGGUCACCGUCUACUAUGGCGUGCCAGUGUGGCGGGACGCCGAUACCACACUGUUCUGC GCCAGCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUGC CAACAGACCCUAAUCCACAGGAGAUCCACCUGGAGAACGUGACAGAGAACUUCAACAUGUGGAA GAACAAGAUGGCCGAGCAGAUGCAGGAGGACGUGAUCUCCCUGUGGGAUGAGUCUCUGAAGCC CUGCGUGCAGCUGACCCCUCUGUGCGUGACACUGAAUUGUACCAAUGCCAACCUGAAUGCCACC GUGAAUGCCUCCACCACAAUCGGCAACAUCACAGAUGAGGUGCGGAACUGUUCUUUCAAUACCA CAACCGAGCUGCGCGACAAGAAGCAGAACGUGUACGCCCUGUUUUAUAAGCUGGAUAUCGUGCC CAUCAACAAUAACUCCGAGUAUCGGCUGAUCAACUGCAAUACCUCUGUGAUCAAGCAGGCCUGU CCUAAGGUGAGCUUCGACCCCAUCCCUAUCCACUACUGCGCACCAGCAGGAUAUGCAAUCCUGC GCUGUAAUGAUAAGAACUUUAAUGGCACAGGCCCCUGCAAGAACGUGAGCUCCGUGCAGUGUA CCCACGGCAUCAAGCCUGUGGUGUCUACACAGCUGCUGCUGAACGGCAGCCUGGCCGAGGACGA GAUCAUCAUCAGGAGCGAGAACCUGACAGAUAAUGUGAAGACCAUCAUCGUGCACCUGAACAAG UCCGUGGAGAUCAAUUGCACCAGGCCAUCUAAUAACACAGUGACCAGCGUGAGAAUCGGCCCCG GCCAGGUGUUCUACUAUACAGGCGACAUCAUCGGCGAUAUCCGGAAGGCCUACUGUGAGAUCA AUCGCACAAAGUGGCACGAGACACUGAAGCAGGUGGCCACCAAGCUGAGGGAGCACUUCAACAA GACAAUCAUCUUUCAGCCCCCUUCCGGCGGCGACAUCGAGAUCACCAUGCACCACUUCAACUGCA GAGGCGAGUUCUUUUACUGUAACACAACCAAGCUGUUUAAUUCUACCUGGGGCGAGAACACAA CCAUGGAGGGCCACAAUGAUACAAUCGUGCUGCCUUGCAGAAUCAAGCAGAUCGUGAACAUGU GGCAGGGAGUGGGACAGGCAAUGUAUGCCCCACCCAUCAGGGGCAGCAUCAACUGCGUGAGCAA UAUCACAGGCAUCCUGCUGACCAGAGACGGCGGAACAAACAUGUCUAAUGAGACAUUCAGGCCU GGCGGCGGCAACAUCAAGGAUAAUUGGAGAAGCGAGCUGUACAAGUAUAAGGUGGUGGAGAUC GAGCCUCUGGGCAUCGCCCCAACAAAGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCG GCGGCUCUGGCAGCGGCGGCCACGCCGCCGUGGGCAUCGGCGCCAUGAGCUUCGGCUUUCUGG GAGCAGCAGGCUCCACCAUGGGAGCAGCCUCUAUCACACUGACCGUGCAGGCAAGGCAGCUGCU GAGCGGCAUCGUGCAGCAGCAGUCCAACCUGCUGAGGGCACCAGAGCCACAGCAGCACCUGCUG CAGGACACCCACUGGGGCAUCAAGCAGCUGCAGGCCCGCGUGCUGGCAGUGGAGCACUACCUGA AGGAUCAGAAGUUUCUGGGCCUGUGGGGCUGUUCCGGCAAGAUCAUCUGCUGUACCGCCGUGC CUUGGAACUCCACAUGGUCUAAUCGGAGCUAUGAGGAGAUCUGGGACAACAUGACCUGGAUCA AUUGGUCCCGCGAGAUCUCUAACUACACAAGCCAGAUCUAUGAGAUCCUGACCGAAUCACAGAA UCAGCAGGACAGAAACAACAAAUCACUGCUGGAACUGGACUGAUAA (SEQ ID NO: 212) CNE55_HM215418_MD39_L14G8 (amino acid, dna, rna) MDWTWILFLVAAATRVHSSDKLWVTVYYGVPVWRDADTTLFCASDAKAHETEVHNVWATHACVPTDP NPQEIHLVNVTENFNMWKNKMVEQMQEDVISLWDESLKPCVKLTPLCVTLNCTTANTNETKNNTTDDN IKDEMKNCTFNMTTEIRDKKQRVSALFYKLDIVPIDDSKNNSEYRLINCNTSVIKQACPKVSFDPIPIHYCTPA GYVILKCNDKNFNGTGPCKNVSSVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNAKNIIVHLNKSVEIN CTRPSNNTVTSVRIGPGQVFYYTGDITGDIRKAYCEIDGTEWNKTLTQVAEKLKEHFNKTIVYQPPSGGDLE ITMHHFNCRGEFFYCNTTQLFNNSVGNSTIKLPCRIKQIINMWQGVGQAMYAPPISGAINCLSNITGILLTR DGGGNNRSNETFRPGGGNIKDNWRSELYKYKVVEIEPLGIAPTKCKRRVVGSHSGSGGSGSGGHAAVGIG AMSFGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLRAPEPQQHMLQDTHWGIKQLQARVLAVE HYLKDQRFLGLWGCSGKTICCTAVPWNSTWSNKTYEEIWDNMTWTNWSREISNYTNQIYSILTESQSQQ DKNNKSLLELD** (SEQ ID NO: 216) atggactggacttggattctgttcctggtcgctgccgctacacgagtgcattcctctgataaactgtgggtgaccgtctactatggagtg ccagtgtggcgggacgccgataccacactgttctgcgcctctgacgccaaggcccacgagacagaggtgcacaacgtgtgggcaac ccacgcatgcgtgccaacagatcctaacccacaggagatccacctggtgaatgtgacagagaactttaatatgtggaagaacaaga tggtggagcagatgcaggaggacgtgatcagcctgtgggatgagtccctgaagccctgcgtgaagctgacccctctgtgcgtgacac tgaactgtaccacagccaacaccaatgagacaaagaacaataccacagacgataatatcaaggacgagatgaagaactgtacctt caatatgaccacagagatccgggacaagaagcagcgcgtgagcgccctgttttacaagctggatatcgtgcccatcgacgatagca agaacaattccgagtatcgcctgatcaactgcaataccagcgtgatcaagcaggcctgtcctaaggtgtccttcgaccccatccctat ccactactgcaccccagccggctatgtgatcctgaagtgtaacgataagaactttaatggcacaggcccctgcaagaatgtgagctc cgtgcagtgtacccacggcatcaagcctgtggtgtccacacagctgctgctgaacggctctctggccgaggaggagatcatcatcag gtctgagaatctgaccgataacgccaagaatatcatcgtgcacctgaacaagagcgtggagatcaattgcacacggccatctaaca ataccgtgacaagcgtgcgcatcggaccaggacaggtgttctactataccggcgacatcacaggcgatatcagaaaggcctactgtg agatcgacggcaccgagtggaacaagaccctgacacaggtggccgagaagctgaaggagcactttaataagaccatcgtgtacca gcccccttccggcggcgatctggagatcacaatgcaccacttcaactgccggggcgagttcttttattgtaataccacacagctgttta acaattctgtgggcaacagcaccatcaagctgccttgccgcatcaagcagatcatcaatatgtggcagggagtgggacaggcaatgt acgccccacccatcagcggagccatcaactgtctgtccaatatcaccggcatcctgctgacaagggacggcggcggaaacaatagg tccaatgagacattcaggcctggcggcggcaacatcaaggataattggagatctgagctgtacaagtataaggtggtggagatcga gcctctgggcatcgccccaacaaagtgcaagaggagagtggtgggctctcacagcggctccggcggctctggcagcggcggccacg ccgccgtgggcatcggcgccatgagcttcggctttctgggagcagcaggctccaccatgggagcagcctctatcaccctgacagtgc aggcccggcagctgctgtctggcatcgtgcagcagcagagcaacctgctgagggcaccagagccacagcagcacatgctgcagga cacacactggggcatcaagcagctgcaggccagggtgctggcagtggagcactacctgaaggatcagagatttctgggcctgtggg gctgtagcggcaagaccatctgctgtacagccgtgccttggaactccacctggtctaataagacatatgaggagatctgggacaaca tgacctggacaaattggtcccgggagatctctaactacaccaatcagatctattccattctgaccgaatcacagtcacagcaggataa aaataacaaaagtctgctggaactggattgataa (SEQ ID NO: 214) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCUGCCGCUACACGAGUGCAUUCCUCUGAUAAA CUGUGGGUGACCGUCUACUAUGGAGUGCCAGUGUGGCGGGACGCCGAUACCACACUGUUCUGC GCCUCUGACGCCAAGGCCCACGAGACAGAGGUGCACAACGUGUGGGCAACCCACGCAUGCGUGC CAACAGAUCCUAACCCACAGGAGAUCCACCUGGUGAAUGUGACAGAGAACUUUAAUAUGUGGAA GAACAAGAUGGUGGAGCAGAUGCAGGAGGACGUGAUCAGCCUGUGGGAUGAGUCCCUGAAGCC CUGCGUGAAGCUGACCCCUCUGUGCGUGACACUGAACUGUACCACAGCCAACACCAAUGAGACA AAGAACAAUACCACAGACGAUAAUAUCAAGGACGAGAUGAAGAACUGUACCUUCAAUAUGACCA CAGAGAUCCGGGACAAGAAGCAGCGCGUGAGCGCCCUGUUUUACAAGCUGGAUAUCGUGCCCA UCGACGAUAGCAAGAACAAUUCCGAGUAUCGCCUGAUCAACUGCAAUACCAGCGUGAUCAAGCA GGCCUGUCCUAAGGUGUCCUUCGACCCCAUCCCUAUCCACUACUGCACCCCAGCCGGCUAUGUG AUCCUGAAGUGUAACGAUAAGAACUUUAAUGGCACAGGCCCCUGCAAGAAUGUGAGCUCCGUG CAGUGUACCCACGGCAUCAAGCCUGUGGUGUCCACACAGCUGCUGCUGAACGGCUCUCUGGCCG AGGAGGAGAUCAUCAUCAGGUCUGAGAAUCUGACCGAUAACGCCAAGAAUAUCAUCGUGCACCU GAACAAGAGCGUGGAGAUCAAUUGCACACGGCCAUCUAACAAUACCGUGACAAGCGUGCGCAUC GGACCAGGACAGGUGUUCUACUAUACCGGCGACAUCACAGGCGAUAUCAGAAAGGCCUACUGU GAGAUCGACGGCACCGAGUGGAACAAGACCCUGACACAGGUGGCCGAGAAGCUGAAGGAGCACU UUAAUAAGACCAUCGUGUACCAGCCCCCUUCCGGCGGCGAUCUGGAGAUCACAAUGCACCACUU CAACUGCCGGGGCGAGUUCUUUUAUUGUAAUACCACACAGCUGUUUAACAAUUCUGUGGGCAA CAGCACCAUCAAGCUGCCUUGCCGCAUCAAGCAGAUCAUCAAUAUGUGGCAGGGAGUGGGACAG GCAAUGUACGCCCCACCCAUCAGCGGAGCCAUCAACUGUCUGUCCAAUAUCACCGGCAUCCUGC UGACAAGGGACGGCGGCGGAAACAAUAGGUCCAAUGAGACAUUCAGGCCUGGCGGCGGCAACA UCAAGGAUAAUUGGAGAUCUGAGCUGUACAAGUAUAAGGUGGUGGAGAUCGAGCCUCUGGGC AUCGCCCCAACAAAGUGCAAGAGGAGAGUGGUGGGCUCUCACAGCGGCUCCGGCGGCUCUGGCA GCGGCGGCCACGCCGCCGUGGGCAUCGGCGCCAUGAGCUUCGGCUUUCUGGGAGCAGCAGGCU CCACCAUGGGAGCAGCCUCUAUCACCCUGACAGUGCAGGCCCGGCAGCUGCUGUCUGGCAUCGU GCAGCAGCAGAGCAACCUGCUGAGGGCACCAGAGCCACAGCAGCACAUGCUGCAGGACACACACU GGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCACUACCUGAAGGAUCAGAGAU UUCUGGGCCUGUGGGGCUGUAGCGGCAAGACCAUCUGCUGUACAGCCGUGCCUUGGAACUCCA CCUGGUCUAAUAAGACAUAUGAGGAGAUCUGGGACAACAUGACCUGGACAAAUUGGUCCCGGG AGAUCUCUAACUACACCAAUCAGAUCUAUUCCAUUCUGACCGAAUCACAGUCACAGCAGGAUAA AAAUAACAAAAGUCUGCUGGAACUGGAUUGAUAA (SEQ ID NO: 215) Other Env sequences Parts of sequences Leader sequences IgE MDWTWILFLVAAATRVHS (SEQ ID NO: 7) AD8: atggactggacttggattctgttcctggtcgccgccgctactcgggtgcattct (SEQ ID NO: 2) 001428: atggactggacttggattctgttcctggtggcagcagcaactagagtgcattcc (SEQ ID NO: 3) Linkers Link 14 (same as MD3) GSHSGSGGSGSGGHA (SEQ ID NO: 13) AD8: tctcacagcggctccggcggctctggcagcggcggccacgcc 001428: ggctcccactctggcagcggcggctccggctctggcggccacgca GS linkers (same as MD39_TS1) AD8:& 001428:& Env parts AD8 gp120 (AD8_MD64_link14 and AD8_MD64_link14_TS1) amino acid, dna, rna VENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDPNPQEVVLENVTENFNMWK NNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLRNVTNINNSSEGMRGEIKNCSFNITTSIRDKVKK DYALFYRLDVVPIDNDNTSYRLINCNTSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGTGPCKNVSTV QCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNNTVKSIHIGPGRAFYYTG DIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIVMHSFNCGGEFFYCNSTQLF NSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEVGKAMYAPPIRGQIRCSSNITGLILTRDGGN NHNNDTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKCKRRVVQ (SEQ ID NO: 61) gtcgaaaacctgtgggtgactgtctattatggagtgcccgtgtggaaggaggccaccacaaccctgttctgcgcctccgacgccaag gcctacgataccgaggtgcacaacgtgtgggccacccacgagtgcgtgcctacagacccaaacccccaggaggtggtgctggaga atgtgacagagaacttcaacatgtggaagaacaatatggtggagcagatgcacgaggacatcatcgagctgtgggatcagagcctg aagccttgcgtgaagctgaccccactgtgcgtgaccctgaattgtacagacctgcggaatgtgacaaacatcaacaatagctccgag ggcatgagaggcgagatcaagaattgtagcttcaacatcacaacctccatcagggacaaggtgaagaaggattacgccctgttttat cgcctggatgtggtgcccatcgacaatgataacacctcttaccggctgatcaattgcaacacaagcaccatcacacaggcctgtcca aaggtgtccttcgagcctatcccaatccactattgcacccccgccggcttcgccatcctgaagtgtaaggacaagaagtttaacggca caggcccttgcaagaacgtgagcaccgtgcagtgtacacacggcatccggccagtggtgagcacccagctgctgctgaacggctcc ctggcagaggaggaagtgatcatcagatctagcaatttcacagataatgccaagaacatcatcgtgcagctgaaggagtccgtgga gatcaactgcacccggcccaacaataacacagtgaagtctatccacatcggccctggcagagccttttactataccggcgacatcatc ggcgatatcaggcaggcccactgtaacatcagccgcaccaagtggaataacacactgaatcagatcgccaccaagctgaaggagc agttcggcaataacaagacaatcgtgtttaaccagtcctctggcggcgacccagagatcgtgatgcactcttttaattgcggcggcga gttcttttactgtaactctacccagctgttcaatagcacatggaacttcaacggcacctggaatctgacacagagcaacggcaccgag ggcaatgataccatcacactgccctgcaggatcaagcagatcatcaacatgtggcaggaagtgggcaaggccatgtatgcccctccc atcaggggccagatccgctgtagctccaatatcaccggcctgatcctgacaagggacggcggaaataaccacaataacgataccga gacattccgccccggcggcggcgacatgagggataactggagatccgagctgtacaagtataaggtggtgaagatcgagccactgg gagtggcaccaaccaagtgcaagaggagagtggtgcag (SEQ ID NO: 59) GUCGAAAACCUGUGGGUGACUGUCUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCACCACAACC CUGUUCUGCGCCUCCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCCACCCACG AGUGCGUGCCUACAGACCCAAACCCCCAGGAGGUGGUGCUGGAGAAUGUGACAGAGAACUUCAA CAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACGAGGACAUCAUCGAGCUGUGGGAUCAGAG CCUGAAGCCUUGCGUGAAGCUGACCCCACUGUGCGUGACCCUGAAUUGUACAGACCUGCGGAA UGUGACAAACAUCAACAAUAGCUCCGAGGGCAUGAGAGGCGAGAUCAAGAAUUGUAGCUUCAAC AUCACAACCUCCAUCAGGGACAAGGUGAAGAAGGAUUACGCCCUGUUUUAUCGCCUGGAUGUG GUGCCCAUCGACAAUGAUAACACCUCUUACCGGCUGAUCAAUUGCAACACAAGCACCAUCACACA GGCCUGUCCAAAGGUGUCCUUCGAGCCUAUCCCAAUCCACUAUUGCACCCCCGCCGGCUUCGCC AUCCUGAAGUGUAAGGACAAGAAGUUUAACGGCACAGGCCCUUGCAAGAACGUGAGCACCGUGC AGUGUACACACGGCAUCCGGCCAGUGGUGAGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAGA GGAGGAAGUGAUCAUCAGAUCUAGCAAUUUCACAGAUAAUGCCAAGAACAUCAUCGUGCAGCU GAAGGAGUCCGUGGAGAUCAACUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCACAUC GGCCCUGGCAGAGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGGCAGGCCCACUGUA ACAUCAGCCGCACCAAGUGGAAUAACACACUGAAUCAGAUCGCCACCAAGCUGAAGGAGCAGUU CGGCAAUAACAAGACAAUCGUGUUUAACCAGUCCUCUGGCGGCGACCCAGAGAUCGUGAUGCAC UCUUUUAAUUGCGGCGGCGAGUUCUUUUACUGUAACUCUACCCAGCUGUUCAAUAGCACAUGG AACUUCAACGGCACCUGGAAUCUGACACAGAGCAACGGCACCGAGGGCAAUGAUACCAUCACACU GCCCUGCAGGAUCAAGCAGAUCAUCAACAUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCCCCU CCCAUCAGGGGCCAGAUCCGCUGUAGCUCCAAUAUCACCGGCCUGAUCCUGACAAGGGACGGCG GAAAUAACCACAAUAACGAUACCGAGACAUUCCGCCCCGGCGGCGGCGACAUGAGGGAUAACUG GAGAUCCGAGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCACUGGGAGUGGCACCAACCAA GUGCAAGAGGAGAGUGGUGCAG (SEQ ID NO: 60) AD8gp41 ecto (AD8_MD64_link14 and AD8_MD64_link14_TS1) (amino acid, dna, rna) AVGTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARV LAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIYTLIEE SQNQQEKNEQELLELD (SEQ ID NO: 89) Gccgtgggcaccatcggcgccatgagcctgggctttctgggagcagcaggctccacaatgggagcagcctctatcaccctgacagt gcaggccaggctgctgctgtccggcatcgtgcagcagcagaataacctgctgagggcaccagagcctcagcagcacctgctgcagc tgaccgtgtggggcatcaagcagctgcaggcccgggtgctggcagtggagcactatctgagagatcagcagctgctgggaatctgg ggatgcagcggcaagctgatctgctgtaccgccgtgccatggaacgcctcctggtctaataagaccctggacatgatctggaataac atgacatggatggagtgggagcgcgagatcgataactacaccggcctgatctatacactgatcgaggaatcacagaatcagcagga gaaaaacgaacaggaactgctggaactggat (SEQ ID NO: 87) GCCGUGGGCACCAUCGGCGCCAUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGA GCAGCCUCUAUCACCCUGACAGUGCAGGCCAGGCUGCUGCUGUCCGGCAUCGUGCAGCAGCAGA AUAACCUGCUGAGGGCACCAGAGCCUCAGCAGCACCUGCUGCAGCUGACCGUGUGGGGCAUCAA GCAGCUGCAGGCCCGGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGAAU CUGGGGAUGCAGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCAUGGAACGCCUCCUGGUCUAA UAAGACCCUGGACAUGAUCUGGAAUAACAUGACAUGGAUGGAGUGGGAGCGCGAGAUCGAUAA CUACACCGGCCUGAUCUAUACACUGAUCGAGGAAUCACAGAAUCAGCAGGAGAAAAACGAACAG GAACUGCUGGAACUGGAU (SEQ ID NO: 88) 001428 gp120 (001428_MD39_link14, 001428_MD39_link14_TS1) (amino acid, dna, rna) VENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDPNPQEMVLGNVTENFNMW KNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTT EIRDKKQKAYALFYRLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNN KTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNNT VKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTSSSGGDLEITTHSFNCR GEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNIT GLLLVRDGGKNNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKRRVV (SEQ ID NO: 64) gtcgaaaacctgtgggtgaccgtgtattatggagtgcccgtgtggaaggaggcccggaccacactgttctgcgcctccgacgccaag gcctacgagacagaggtgcacaacgtgtgggccacacacgcctgcgtgcctaccgatccaaatccccaggagatggtgctgggcaa cgtgaccgagaactttaatatgtggaagaacgacatggtggatcagatgcacgaggacgtgatctctctgtgggcccagagcctgaa gccttgcgtgaagctgaccccactgtgcgtgacactggagtgtacccaggtgaacgccacacagggcaataccacacaggtgaacg tgacccaagtgaatggcgacgagatgaagaactgttccttcaataccacaaccgagatccgggataagaagcagaaggcctacgcc ctgttttatagactggacctggtgcctctggagcgggagaacagaggcgattctaatagcgcctccaagtatatcctgatcaactgca atacatctgccatcacccaggcctgtcctaaagtgaatttcgatcctatcccaatccactactgcaccccagccggctatgccatcctg aagtgtaacaacaagaccttcaacggcaccggctcctgcaacaacgtgagcacagtgcagtgtacccacggcatcaagccagtggt gagcacccagctgctgctgaacggctccctggcagaggaggagatcatcatcaggtccgagaacctgacagacaatgtgaagacc atcatcgtgcacctggatcagtccgtggagatcgtgtgcacacggccaaacaataacaccgtgaagtctatcagaatcggccccggc cagacattctactataccggcgacatcatcggcaatatccgggaggcccactgtaacatctctgagaagaagtggcacgagatgctg cggagagtgagcgagaagctggccgagcacttccccaataagacaatcaagtttaccagctcctctggcggcgatctggagatcac aacccacagcttcaactgcagaggcgagttcttttactgtaacaccagcggcctgtttaattccacatacatgcccaacggcacctata tgcctaatggcacaaataactctaacagcaccatcatcctgccatgccggatcaagcagatcatcaatatgtggcaggaagtgggca gagccatgtatgcccctcccatcgccggcaacatcacatgtaacagcaatatcaccggcctgctgctggtgagggacggcggcaag aataacaatacagagatcttccgccccggcggcggcgacatgagggataactggcgctccgagctgtacaagtataaggtggtgga gatcaagccactgggagtggcaccaaccaggtgcaagaggcgcgtggtg (SEQ ID NO: 62) GUCGAAAACCUGUGGGUGACCGUGUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCCGGACCACA CUGUUCUGCGCCUCCGACGCCAAGGCCUACGAGACAGAGGUGCACAACGUGUGGGCCACACACG CCUGCGUGCCUACCGAUCCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGACCGAGAACUUUAA UAUGUGGAAGAACGACAUGGUGGAUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGCCCAGAG CCUGAAGCCUUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUACCCAGGUGAACGCC ACACAGGGCAAUACCACACAGGUGAACGUGACCCAAGUGAAUGGCGACGAGAUGAAGAACUGUU CCUUCAAUACCACAACCGAGAUCCGGGAUAAGAAGCAGAAGGCCUACGCCCUGUUUUAUAGACU GGACCUGGUGCCUCUGGAGCGGGAGAACAGAGGCGAUUCUAAUAGCGCCUCCAAGUAUAUCCU GAUCAACUGCAAUACAUCUGCCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGAUCCUAUCCCA AUCCACUACUGCACCCCAGCCGGCUAUGCCAUCCUGAAGUGUAACAACAAGACCUUCAACGGCAC CGGCUCCUGCAACAACGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCAGUGGUGAGCACC CAGCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAGAUCAUCAUCAGGUCCGAGAACCUGACAG ACAAUGUGAAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGAGAUCGUGUGCACACGGCCAAA CAAUAACACCGUGAAGUCUAUCAGAAUCGGCCCCGGCCAGACAUUCUACUAUACCGGCGACAUC AUCGGCAAUAUCCGGGAGGCCCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGAUGCUGCGG AGAGUGAGCGAGAAGCUGGCCGAGCACUUCCCCAAUAAGACAAUCAAGUUUACCAGCUCCUCUG GCGGCGAUCUGGAGAUCACAACCCACAGCUUCAACUGCAGAGGCGAGUUCUUUUACUGUAACAC CAGCGGCCUGUUUAAUUCCACAUACAUGCCCAACGGCACCUAUAUGCCUAAUGGCACAAAUAAC UCUAACAGCACCAUCAUCCUGCCAUGCCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAGUGG GCAGAGCCAUGUAUGCCCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCAAUAUCACCGGCCUG CUGCUGGUGAGGGACGGCGGCAAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGGCGGCGACA UGAGGGAUAACUGGCGCUCCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGAG UGGCACCAACCAGGUGCAAGAGGCGCGUGGUG (SEQ ID NO: 63) 001428 gp41 ecto (001428_MD39_link14_(,) 001428_MD39_link14_TS1) (amino acid, dna, rna) AVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRV LAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWMQWDREVSNYTGIIYRLLEDS QNQQERNEQDLLALD (SEQ ID NO: 92) Gcagtgggcctgggagccgtgagcctgggctttctgggagcagcaggctctaccatgggagcagccagcatcacactgaccgtgca ggcaaggcagctgctgtccggcatcgtgcagcagcagtctaacctgctgcaggcaccagagcctcagcagcacctgctgcaggaca cacactggggcatcaagcagctgcagacccgcgtgctggccatcgagcactacctgaaggatcagcagctgctgggcatctggggc tgctctggcaagctgatctgctgtacagccgtgccttggaacagctcctggagcaataagtccctgacagacatctgggataatatga cctggatgcagtgggatagggaggtgagcaactacaccggcatcatctatcgcctgctggaagactcacagaatcagcaggaaagg aatgaacaggatctgctggcactggac (SEQ ID NO: 90) GCAGUGGGCCUGGGAGCCGUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCUACCAUGGGAGCA GCCAGCAUCACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGGCAUCGUGCAGCAGCAGUCUA ACCUGCUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCAGGACACACACUGGGGCAUCAAGCA GCUGCAGACCCGCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUG GGGCUGCUCUGGCAAGCUGAUCUGCUGUACAGCCGUGCCUUGGAACAGCUCCUGGAGCAAUAA GUCCCUGACAGACAUCUGGGAUAAUAUGACCUGGAUGCAGUGGGAUAGGGAGGUGAGCAACUA CACCGGCAUCAUCUAUCGCCUGCUGGAAGACUCACAGAAUCAGCAGGAAAGGAAUGAACAGGAU CUGCUGGCACUGGAC (SEQ ID NO: 91) Full length sequences AD8_MD64_link14 (amino acid, dna, rna) MDWTWILFLVAAATRVHSVENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDP NPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLRNVTNINNSSEGM RGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINCNTSTITQACPKVSFEPIPIHYCTPAGFAIL KCKDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRP NNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIV MHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEVGKAMYAPPI RGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKCKRVVQS HSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLL QLTVWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEW EREIDNYTGLIYTLIEESQNQQEKNEQELLELD** (SEQ ID NO: 219) atggactggacttggattctgttcctggtcgccgccgctactcgggtgcattctgtcgaaaacctgtgggtgactgtctattatggagtg cccgtgtggaaggaggccaccacaaccctgttctgcgcctccgacgccaaggcctacgataccgaggtgcacaacgtgtgggccac ccacgagtgcgtgcctacagacccaaacccccaggaggtggtgctggagaatgtgacagagaacttcaacatgtggaagaacaat atggtggagcagatgcacgaggacatcatcgagctgtgggatcagagcctgaagccttgcgtgaagctgaccccactgtgcgtgac cctgaattgtacagacctgcggaatgtgacaaacatcaacaatagctccgagggcatgagaggcgagatcaagaattgtagcttca acatcacaacctccatcagggacaaggtgaagaaggattacgccctgttttatcgcctggatgtggtgcccatcgacaatgataaca cctcttaccggctgatcaattgcaacacaagcaccatcacacaggcctgtccaaaggtgtccttcgagcctatcccaatccactattgc acccccgccggcttcgccatcctgaagtgtaaggacaagaagtttaacggcacaggcccttgcaagaacgtgagcaccgtgcagtgt acacacggcatccggccagtggtgagcacccagctgctgctgaacggctccctggcagaggaggaagtgatcatcagatctagcaa tttcacagataatgccaagaacatcatcgtgcagctgaaggagtccgtggagatcaactgcacccggcccaacaataacacagtga agtctatccacatcggccctggcagagccttttactataccggcgacatcatcggcgatatcaggcaggcccactgtaacatcagccg caccaagtggaataacacactgaatcagatcgccaccaagctgaaggagcagttcggcaataacaagacaatcgtgtttaaccagt cctctggcggcgacccagagatcgtgatgcactcttttaattgcggcggcgagttcttttactgtaactctacccagctgttcaatagca catggaacttcaacggcacctggaatctgacacagagcaacggcaccgagggcaatgataccatcacactgccctgcaggatcaag cagatcatcaacatgtggcaggaagtgggcaaggccatgtatgcccctcccatcaggggccagatccgctgtagctccaatatcacc ggcctgatcctgacaagggacggcggaaataaccacaataacgataccgagacattccgccccggcggcggcgacatgagggata actggagatccgagctgtacaagtataaggtggtgaagatcgagccactgggagtggcaccaaccaagtgcaagaggagagtggt gcagtctcacagcggctccggcggctctggcagcggcggccacgccgccgtgggcaccatcggcgccatgagcctgggctttctggg agcagcaggctccacaatgggagcagcctctatcaccctgacagtgcaggccaggctgctgctgtccggcatcgtgcagcagcaga ataacctgctgagggcaccagagcctcagcagcacctgctgcagctgaccgtgtggggcatcaagcagctgcaggcccgggtgctg gcagtggagcactatctgagagatcagcagctgctgggaatctggggatgcagcggcaagctgatctgctgtaccgccgtgccatgg aacgcctcctggtctaataagaccctggacatgatctggaataacatgacatggatggagtgggagcgcgagatcgataactacacc ggcctgatctatacactgatcgaggaatcacagaatcagcaggagaaaaacgaacaggaactgctggaactggattgataa (SEQ ID NO: 217) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGCCGCUACUCGGGUGCAUUCUGUCGAAAAC CUGUGGGUGACUGUCUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCUCCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCCACCCACGAGUGCGUGC CUACAGACCCAAACCCCCAGGAGGUGGUGCUGGAGAAUGUGACAGAGAACUUCAACAUGUGGAA GAACAAUAUGGUGGAGCAGAUGCACGAGGACAUCAUCGAGCUGUGGGAUCAGAGCCUGAAGCC UUGCGUGAAGCUGACCCCACUGUGCGUGACCCUGAAUUGUACAGACCUGCGGAAUGUGACAAA CAUCAACAAUAGCUCCGAGGGCAUGAGAGGCGAGAUCAAGAAUUGUAGCUUCAACAUCACAACC UCCAUCAGGGACAAGGUGAAGAAGGAUUACGCCCUGUUUUAUCGCCUGGAUGUGGUGCCCAUC GACAAUGAUAACACCUCUUACCGGCUGAUCAAUUGCAACACAAGCACCAUCACACAGGCCUGUCC AAAGGUGUCCUUCGAGCCUAUCCCAAUCCACUAUUGCACCCCCGCCGGCUUCGCCAUCCUGAAG UGUAAGGACAAGAAGUUUAACGGCACAGGCCCUUGCAAGAACGUGAGCACCGUGCAGUGUACAC ACGGCAUCCGGCCAGUGGUGAGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAAG UGAUCAUCAGAUCUAGCAAUUUCACAGAUAAUGCCAAGAACAUCAUCGUGCAGCUGAAGGAGUC CGUGGAGAUCAACUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCACAUCGGCCCUGGC AGAGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGGCAGGCCCACUGUAACAUCAGCC GCACCAAGUGGAAUAACACACUGAAUCAGAUCGCCACCAAGCUGAAGGAGCAGUUCGGCAAUAA CAAGACAAUCGUGUUUAACCAGUCCUCUGGCGGCGACCCAGAGAUCGUGAUGCACUCUUUUAA UUGCGGCGGCGAGUUCUUUUACUGUAACUCUACCCAGCUGUUCAAUAGCACAUGGAACUUCAA CGGCACCUGGAAUCUGACACAGAGCAACGGCACCGAGGGCAAUGAUACCAUCACACUGCCCUGCA GGAUCAAGCAGAUCAUCAACAUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCCCCUCCCAUCAG GGGCCAGAUCCGCUGUAGCUCCAAUAUCACCGGCCUGAUCCUGACAAGGGACGGCGGAAAUAAC CACAAUAACGAUACCGAGACAUUCCGCCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUCCG AGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCACUGGGAGUGGCACCAACCAAGUGCAAGA GGAGAGUGGUGCAGUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCCACGCCGCCGUGG GCACCAUCGGCGCCAUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUC UAUCACCCUGACAGUGCAGGCCAGGCUGCUGCUGUCCGGCAUCGUGCAGCAGCAGAAUAACCUG CUGAGGGCACCAGAGCCUCAGCAGCACCUGCUGCAGCUGACCGUGUGGGGCAUCAAGCAGCUGC AGGCCCGGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGAAUCUGGGGAU GCAGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCAUGGAACGCCUCCUGGUCUAAUAAGACCCU GGACAUGAUCUGGAAUAACAUGACAUGGAUGGAGUGGGAGCGCGAGAUCGAUAACUACACCGG CCUGAUCUAUACACUGAUCGAGGAAUCACAGAAUCAGCAGGAGAAAAACGAACAGGAACUGCUG GAACUGGAUUGAUAA (SEQ ID NO: 218) AD8_MD64_link14_TS1 (amino acid, dna, rna) Repeat 1 optimized for human Repeat 2 optimized for human/mouse Repeat 3 optimized for mouse to prevent recombination and large repeats on the nucleic acid level MDWTWILFLVAAATRVHSVENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVHNVWATHECVPTDP NPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTDLRNVTNINNSSEGM RGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINCNTSTITQACPKVSFEPIPIHYCTPAGFAIL KCKDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNIIVQLKESVEINCTRP NNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKTIVFNQSSGGDPEIV MHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINMWQEVGKAMYAPPI RGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKCKRRVVQS HSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQNNLLRAPEPQQHLL QLTVWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLDMIWNNMTWMEW EREIDNYTGLIYTLIEESQNQQEKNEQELLELDGGVENLWVTVYYGVPVWKEATTTLFCASDAKAYDTEVH NVWATHECVPTDPNPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKPCVKLTPLCVTLNCTD LRNVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLINCNTSTITQACPKVSF EPIPIHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVIIRSSNFTDNAKNII VQLKESVEINCTRPNNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTLNQIATKLKEQFGNNKT IVFNQSSGGDPEIVMHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTEGNDTITLPCRIKQIINM WQEVGKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRDNWRSELYKYKVVKIEPL GVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMGAASITLTVQARLLLSGIVQQQ NNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCTAVPWNASWSNKTLD MIWNNMTWMEWEREIDNYTGLIYTLIEESQNQQEKNEQELLELDGGVENLWVTVYYGVPVWKEATTTL FCASDAKAYDTEVHNVWATHECVPTDPNPQEVVLENVTENFNMWKNNMVEQMHEDIIELWDQSLKP CVKLTPLCVTLNCTDLRNVTNINNSSEGMRGEIKNCSFNITTSIRDKVKKDYALFYRLDVVPIDNDNTSYRLI NCNTSTITQACPKVSFEPIPIHYCTPAGFAILKCKDKKFNGTGPCKNVSTVQCTHGIRPVVSTQLLLNGSLAE EEVIIRSSNFTDNAKNIIVQLKESVEINCTRPNNNTVKSIHIGPGRAFYYTGDIIGDIRQAHCNISRTKWNNTL NQIATKLKEQFGNNKTIVFNQSSGGDPEIVMHSFNCGGEFFYCNSTQLFNSTWNFNGTWNLTQSNGTE GNDTITLPCRIKQIINMWQEVGKAMYAPPIRGQIRCSSNITGLILTRDGGNNHNNDTETFRPGGGDMRD NWRSELYKYKVVKIEPLGVAPTKCKRRVVQSHSGSGGSGSGGHAAVGTIGAMSLGFLGAAGSTMGAASIT LTVQARLLLSGIVQQQNNLLRAPEPQQHLLQLTVWGIKQLQARVLAVEHYLRDQQLLGIWGCSGKLICCT AVPWNASWSNKTLDMIWNNMTWMEWEREIDNYTGLIYTLIEESQNQQEKNEQELLELD** (SEQ ID NO: 222) atggactggacttggattctgttcctggtcgccgccgctactcgggtgcattctgtcgaaaacctgtgggtgactgtctattatggagtg cccgtgtggaaggaggccaccacaaccctgttctgcgcctccgacgccaaggcctacgataccgaggtgcacaacgtgtgggccac ccacgagtgcgtgcctacagacccaaacccccaggaggtggtgctggagaatgtgacagagaacttcaacatgtggaagaacaat atggtggagcagatgcacgaggacatcatcgagctgtgggatcagagcctgaagccttgcgtgaagctgaccccactgtgcgtgac cctgaattgtacagacctgcggaatgtgacaaacatcaacaatagctccgagggcatgagaggcgagatcaagaattgtagcttca acatcacaacctccatcagggacaaggtgaagaaggattacgccctgttttatcgcctggatgtggtgcccatcgacaatgataaca cctcttaccggctgatcaattgcaacacaagcaccatcacacaggcctgtccaaaggtgtccttcgagcctatcccaatccactattgc acccccgccggcttcgccatcctgaagtgtaaggacaagaagtttaacggcacaggcccttgcaagaacgtgagcaccgtgcagtgt acacacggcatccggccagtggtgagcacccagctgctgctgaacggctccctggcagaggaggaagtgatcatcagatctagcaa tttcacagataatgccaagaacatcatcgtgcagctgaaggagtccgtggagatcaactgcacccggcccaacaataacacagtga agtctatccacatcggccctggcagagccttttactataccggcgacatcatcggcgatatcaggcaggcccactgtaacatcagccg caccaagtggaataacacactgaatcagatcgccaccaagctgaaggagcagttcggcaataacaagacaatcgtgtttaaccagt cctctggcggcgacccagagatcgtgatgcactcttttaattgcggcggcgagttcttttactgtaactctacccagctgttcaatagca catggaacttcaacggcacctggaatctgacacagagcaacggcaccgagggcaatgataccatcacactgccctgcaggatcaag cagatcatcaacatgtggcaggaagtgggcaaggccatgtatgcccctcccatcaggggccagatccgctgtagctccaatatcacc ggcctgatcctgacaagggacggcggaaataaccacaataacgataccgagacattccgccccggcggcggcgacatgagggata actggagatccgagctgtacaagtataaggtggtgaagatcgagccactgggagtggcaccaaccaagtgcaagaggagagtggt gcagtctcacagcggctccggcggctctggcagcggcggccacgccgccgtgggcaccatcggcgccatgagcctgggctttctggg agcagcaggctccacaatgggagcagcctctatcaccctgacagtgcaggccaggctgctgctgtccggcatcgtgcagcagcaga ataacctgctgagggcaccagagcctcagcagcacctgctgcagctgaccgtgtggggcatcaagcagctgcaggcccgggtgctg gcagtggagcactatctgagagatcagcagctgctgggaatctggggatgcagcggcaagctgatctgctgtaccgccgtgccatgg aacgcctcctggtctaataagaccctggacatgatctggaataacatgacatggatggagtgggagcgcgagatcgataactacacc ggcctgatctatacactgatcgaggaatcacagaatcagcaggagaaaaacgaacaggaactgctggaactggatgtcgaaaatct ctgggtcaccgtctattatggggtccctgtctggaaggaagcaactactactctgttctgtgcctccgatgccaaggcctacgacacag aggtgcacaacgtgtgggctacacacgagtgcgtgccaaccgatccaaacccccaggaggtggtgctggagaacgtgaccgagaa cttcaacatgtggaagaacaacatggtggagcagatgcacgaggacatcatcgagctgtgggatcagtccctgaagccttgcgtga agctgacaccactgtgcgtgacactgaactgtaccgacctgaggaacgtgaccaacatcaacaacagctccgagggaatgagagg cgagatcaagaactgtagcttcaacatcaccacatccatccgggacaaggtgaagaaggattacgccctgttttaccgcctggatgt ggtgcccatcgacaacgataacacctcttacaggctgatcaactgcaacaccagcacaatcacccaggcttgtccaaaggtgtccttt gagcctatcccaatccactactgcacacccgccggcttcgctatcctgaagtgtaaggacaagaagtttaacggaaccggcccttgc aagaacgtgtctacagtgcagtgtacccacggcatcaggccagtggtgagcacacagctgctgctgaacggcagcctggccgagga ggaagtgatcatcagatctagcaacttcaccgataacgctaagaacatcatcgtgcagctgaaggagtccgtggagatcaactgcac aaggcccaacaacaacaccgtgaagtctatccacatcggacctggcagagccttttactacacaggagacatcatcggcgatatccg gcaggctcactgtaacatcagccgcacaaagtggaacaacaccctgaaccagatcgccacaaagctgaaggagcagttcggcaac aacaagaccatcgtgtttaaccagtccagcggcggcgaccccgagatcgtgatgcactctttcaactgcggcggagagttcttttact gtaactctacacagctgttcaacagcacctggaactttaacggaacatggaacctgacccagagcaacggaaccgagggcaacgat acaatcaccctgccttgccggatcaagcagatcatcaacatgtggcaggaagtgggaaaggccatgtacgctccccctatcagggg acagatcaggtgtagctccaacatcacaggactgatcctgacccgggacggcggaaacaaccacaacaacgatacagagacattc aggcctggcggaggcgacatgagggataactggagatccgagctgtacaagtacaaggtggtgaagatcgagccactgggagtgg ctccaaccaagtgcaagaggagagtggtgcagtctcacagcggcagcggcggcagcggcagcggaggccacgctgctgtgggaac aatcggagctatgagcctgggatttctgggagctgctggcagcaccatgggagctgcttctatcacactgaccgtgcaggctaggctg ctgctgtccggaatcgtgcagcagcagaacaacctgctgagggctccagagcctcagcagcacctgctgcagctgacagtgtgggg catcaagcagctgcaggccagggtgctggctgtggagcactacctgagggaccagcagctgctgggcatctggggatgtagcggca agctgatctgctgtaccgccgtgccatggaacgcttcctggtctaacaagacactggacatgatctggaacaacatgacctggatgg agtgggagcgcgagatcgataactacacaggcctgatctacaccctgatcgaagaaagtcagaatcagcaggaaaagaacgaaca ggaactgctggaactggacgtcgagaatctgtgggtcaccgtctattatggagtccccgtctggaaagaggctactactacactgtttt gtgcaagcgatgccaaggcctacgacacagaggtgcacaacgtgtgggccacacacgagtgcgtgccaaccgatccaaaccccca ggaggtggtgctggagaatgtgaccgagaatttcaacatgtggaagaacaatatggtggagcagatgcacgaggacatcatcgagc tgtgggatcagtccctgaagccttgcgtgaagctgacaccactgtgcgtgacactgaactgtaccgacctgaggaatgtgaccaaca tcaacaatagctccgagggcatgagaggcgagatcaagaattgtagcttcaacatcaccacatccatccgggacaaggtgaagaag gattacgccctgttttatcgcctggatgtggtgcccatcgacaatgataacacctcttacaggctgatcaattgcaacaccagcacaat cacccaggcctgtccaaaggtgtcctttgagcctatcccaatccactattgcacacccgccggcttcgccatcctgaagtgtaaggac aagaagtttaacggcaccggcccttgcaagaacgtgagcacagtgcagtgtacccacggcatcaggccagtggtgagcacacagct gctgctgaacggctccctggccgaggaggaagtgatcatcagatctagcaatttcaccgataatgccaagaacatcatcgtgcagct gaaggagtccgtggagatcaactgcacaaggcccaacaataacaccgtgaagtctatccacatcggccctggcagagccttttacta taccggcgacatcatcggcgatatccggcaggcccactgtaacatcagccgcacaaagtggaataacaccctgaatcagatcgcca caaagctgaaggagcagttcggcaataacaagaccatcgtgtttaaccagtcctctggcggcgaccccgagatcgtgatgcactcttt caattgcggcggcgagttcttttactgtaactctacacagctgttcaatagcacctggaacttcaacggcacatggaatctgacccag agcaacggcaccgagggcaatgatacaatcaccctgccttgccggatcaagcagatcatcaacatgtggcaggaagtgggcaagg ccatgtatgcccctcccatcaggggacagatcaggtgtagctccaatatcacaggcctgatcctgacccgggacggcggaaataacc acaataacgatacagagacattcaggcccggcggcggcgacatgagggataactggagatccgagctgtacaagtataaggtggt gaagatcgagccactgggagtggcaccaaccaagtgcaagaggagagtggtgcagtctcacagcggctccggcggctctggcagc ggcggccacgcagcagtgggaacaatcggagcaatgagcctgggctttctgggagcagcaggctccaccatgggagcagcctctat cacactgaccgtgcaggcaaggctgctgctgtccggcatcgtgcagcagcagaataacctgctgagggcaccagagcctcagcagc acctgctgcagctgacagtgtggggcatcaagcagctgcaggccagggtgctggcagtggagcactatctgagggaccagcagctg ctgggcatctggggctgtagcggcaagctgatctgctgtaccgccgtgccctggaacgcctcctggtctaataagacactggacatga tctggaataacatgacctggatggagtgggagcgcgagatcgataactacacaggcctgatctataccctgattgaggagtcacaga accagcaggaaaagaacgaacaggaactgctggaactggattgataa (SEQ ID NO: 220) AUGGACUGGACUUGGAUUCUGUUCCUGGUCGCCGCCGCUACUCGGGUGCAUUCUGUCGAAAAC CUGUGGGUGACUGUCUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCACCACAACCCUGUUCUGC GCCUCCGACGCCAAGGCCUACGAUACCGAGGUGCACAACGUGUGGGCCACCCACGAGUGCGUGC CUACAGACCCAAACCCCCAGGAGGUGGUGCUGGAGAAUGUGACAGAGAACUUCAACAUGUGGAA GAACAAUAUGGUGGAGCAGAUGCACGAGGACAUCAUCGAGCUGUGGGAUCAGAGCCUGAAGCC UUGCGUGAAGCUGACCCCACUGUGCGUGACCCUGAAUUGUACAGACCUGCGGAAUGUGACAAA CAUCAACAAUAGCUCCGAGGGCAUGAGAGGCGAGAUCAAGAAUUGUAGCUUCAACAUCACAACC UCCAUCAGGGACAAGGUGAAGAAGGAUUACGCCCUGUUUUAUCGCCUGGAUGUGGUGCCCAUC GACAAUGAUAACACCUCUUACCGGCUGAUCAAUUGCAACACAAGCACCAUCACACAGGCCUGUCC AAAGGUGUCCUUCGAGCCUAUCCCAAUCCACUAUUGCACCCCCGCCGGCUUCGCCAUCCUGAAG UGUAAGGACAAGAAGUUUAACGGCACAGGCCCUUGCAAGAACGUGAGCACCGUGCAGUGUACAC ACGGCAUCCGGCCAGUGGUGAGCACCCAGCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAAG UGAUCAUCAGAUCUAGCAAUUUCACAGAUAAUGCCAAGAACAUCAUCGUGCAGCUGAAGGAGUC CGUGGAGAUCAACUGCACCCGGCCCAACAAUAACACAGUGAAGUCUAUCCACAUCGGCCCUGGC AGAGCCUUUUACUAUACCGGCGACAUCAUCGGCGAUAUCAGGCAGGCCCACUGUAACAUCAGCC GCACCAAGUGGAAUAACACACUGAAUCAGAUCGCCACCAAGCUGAAGGAGCAGUUCGGCAAUAA CAAGACAAUCGUGUUUAACCAGUCCUCUGGCGGCGACCCAGAGAUCGUGAUGCACUCUUUUAA UUGCGGCGGCGAGUUCUUUUACUGUAACUCUACCCAGCUGUUCAAUAGCACAUGGAACUUCAA CGGCACCUGGAAUCUGACACAGAGCAACGGCACCGAGGGCAAUGAUACCAUCACACUGCCCUGCA GGAUCAAGCAGAUCAUCAACAUGUGGCAGGAAGUGGGCAAGGCCAUGUAUGCCCCUCCCAUCAG GGGCCAGAUCCGCUGUAGCUCCAAUAUCACCGGCCUGAUCCUGACAAGGGACGGCGGAAAUAAC CACAAUAACGAUACCGAGACAUUCCGCCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUCCG AGCUGUACAAGUAUAAGGUGGUGAAGAUCGAGCCACUGGGAGUGGCACCAACCAAGUGCAAGA GGAGAGUGGUGCAGUCUCACAGCGGCUCCGGCGGCUCUGGCAGCGGCGGCCACGCCGCCGUGG GCACCAUCGGCGCCAUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCCACAAUGGGAGCAGCCUC UAUCACCCUGACAGUGCAGGCCAGGCUGCUGCUGUCCGGCAUCGUGCAGCAGCAGAAUAACCUG CUGAGGGCACCAGAGCCUCAGCAGCACCUGCUGCAGCUGACCGUGUGGGGCAUCAAGCAGCUGC AGGCCCGGGUGCUGGCAGUGGAGCACUAUCUGAGAGAUCAGCAGCUGCUGGGAAUCUGGGGAU GCAGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCAUGGAACGCCUCCUGGUCUAAUAAGACCCU GGACAUGAUCUGGAAUAACAUGACAUGGAUGGAGUGGGAGCGCGAGAUCGAUAACUACACCGG CCUGAUCUAUACACUGAUCGAGGAAUCACAGAAUCAGCAGGAGAAAAACGAACAGGAACUGCUG GAACUGGAUGUCGAAAAUCUCUGGGUCACCGUCUAUUAUGGGGUCCCUGUCUGGAAGGAAGCA ACUACUACUCUGUUCUGUGCCUCCGAUGCCAAGGCCUACGACACAGAGGUGCACAACGUGUGG GCUACACACGAGUGCGUGCCAACCGAUCCAAACCCCCAGGAGGUGGUGCUGGAGAACGUGACCG AGAACUUCAACAUGUGGAAGAACAACAUGGUGGAGCAGAUGCACGAGGACAUCAUCGAGCUGU GGGAUCAGUCCCUGAAGCCUUGCGUGAAGCUGACACCACUGUGCGUGACACUGAACUGUACCG ACCUGAGGAACGUGACCAACAUCAACAACAGCUCCGAGGGAAUGAGAGGCGAGAUCAAGAACUG UAGCUUCAACAUCACCACAUCCAUCCGGGACAAGGUGAAGAAGGAUUACGCCCUGUUUUACCGC CUGGAUGUGGUGCCCAUCGACAACGAUAACACCUCUUACAGGCUGAUCAACUGCAACACCAGCA CAAUCACCCAGGCUUGUCCAAAGGUGUCCUUUGAGCCUAUCCCAAUCCACUACUGCACACCCGCC GGCUUCGCUAUCCUGAAGUGUAAGGACAAGAAGUUUAACGGAACCGGCCCUUGCAAGAACGUG UCUACAGUGCAGUGUACCCACGGCAUCAGGCCAGUGGUGAGCACACAGCUGCUGCUGAACGGCA GCCUGGCCGAGGAGGAAGUGAUCAUCAGAUCUAGCAACUUCACCGAUAACGCUAAGAACAUCAU CGUGCAGCUGAAGGAGUCCGUGGAGAUCAACUGCACAAGGCCCAACAACAACACCGUGAAGUCU AUCCACAUCGGACCUGGCAGAGCCUUUUACUACACAGGAGACAUCAUCGGCGAUAUCCGGCAGG CUCACUGUAACAUCAGCCGCACAAAGUGGAACAACACCCUGAACCAGAUCGCCACAAAGCUGAAG GAGCAGUUCGGCAACAACAAGACCAUCGUGUUUAACCAGUCCAGCGGCGGCGACCCCGAGAUCG UGAUGCACUCUUUCAACUGCGGCGGAGAGUUCUUUUACUGUAACUCUACACAGCUGUUCAACA GCACCUGGAACUUUAACGGAACAUGGAACCUGACCCAGAGCAACGGAACCGAGGGCAACGAUAC AAUCACCCUGCCUUGCCGGAUCAAGCAGAUCAUCAACAUGUGGCAGGAAGUGGGAAAGGCCAUG UACGCUCCCCCUAUCAGGGGACAGAUCAGGUGUAGCUCCAACAUCACAGGACUGAUCCUGACCC GGGACGGCGGAAACAACCACAACAACGAUACAGAGACAUUCAGGCCUGGCGGAGGCGACAUGAG GGAUAACUGGAGAUCCGAGCUGUACAAGUACAAGGUGGUGAAGAUCGAGCCACUGGGAGUGGC UCCAACCAAGUGCAAGAGGAGAGUGGUGCAGUCUCACAGCGGCAGCGGCGGCAGCGGCAGCGGA GGCCACGCUGCUGUGGGAACAAUCGGAGCUAUGAGCCUGGGAUUUCUGGGAGCUGCUGGCAGC ACCAUGGGAGCUGCUUCUAUCACACUGACCGUGCAGGCUAGGCUGCUGCUGUCCGGAAUCGUG CAGCAGCAGAACAACCUGCUGAGGGCUCCAGAGCCUCAGCAGCACCUGCUGCAGCUGACAGUGU GGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCUGUGGAGCACUACCUGAGGGACCAGCAGC UGCUGGGCAUCUGGGGAUGUAGCGGCAAGCUGAUCUGCUGUACCGCCGUGCCAUGGAACGCUU CCUGGUCUAACAAGACACUGGACAUGAUCUGGAACAACAUGACCUGGAUGGAGUGGGAGCGCG AGAUCGAUAACUACACAGGCCUGAUCUACACCCUGAUCGAAGAAAGUCAGAAUCAGCAGGAAAA GAACGAACAGGAACUGCUGGAACUGGACGUCGAGAAUCUGUGGGUCACCGUCUAUUAUGGAGU CCCCGUCUGGAAAGAGGCUACUACUACACUGUUUUGUGCAAGCGAUGCCAAGGCCUACGACACA GAGGUGCACAACGUGUGGGCCACACACGAGUGCGUGCCAACCGAUCCAAACCCCCAGGAGGUGG UGCUGGAGAAUGUGACCGAGAAUUUCAACAUGUGGAAGAACAAUAUGGUGGAGCAGAUGCACG AGGACAUCAUCGAGCUGUGGGAUCAGUCCCUGAAGCCUUGCGUGAAGCUGACACCACUGUGCG UGACACUGAACUGUACCGACCUGAGGAAUGUGACCAACAUCAACAAUAGCUCCGAGGGCAUGAG AGGCGAGAUCAAGAAUUGUAGCUUCAACAUCACCACAUCCAUCCGGGACAAGGUGAAGAAGGAU UACGCCCUGUUUUAUCGCCUGGAUGUGGUGCCCAUCGACAAUGAUAACACCUCUUACAGGCUG AUCAAUUGCAACACCAGCACAAUCACCCAGGCCUGUCCAAAGGUGUCCUUUGAGCCUAUCCCAA UCCACUAUUGCACACCCGCCGGCUUCGCCAUCCUGAAGUGUAAGGACAAGAAGUUUAACGGCAC CGGCCCUUGCAAGAACGUGAGCACAGUGCAGUGUACCCACGGCAUCAGGCCAGUGGUGAGCACA CAGCUGCUGCUGAACGGCUCCCUGGCCGAGGAGGAAGUGAUCAUCAGAUCUAGCAAUUUCACC GAUAAUGCCAAGAACAUCAUCGUGCAGCUGAAGGAGUCCGUGGAGAUCAACUGCACAAGGCCCA ACAAUAACACCGUGAAGUCUAUCCACAUCGGCCCUGGCAGAGCCUUUUACUAUACCGGCGACAU CAUCGGCGAUAUCCGGCAGGCCCACUGUAACAUCAGCCGCACAAAGUGGAAUAACACCCUGAAU CAGAUCGCCACAAAGCUGAAGGAGCAGUUCGGCAAUAACAAGACCAUCGUGUUUAACCAGUCCU CUGGCGGCGACCCCGAGAUCGUGAUGCACUCUUUCAAUUGCGGCGGCGAGUUCUUUUACUGUA ACUCUACACAGCUGUUCAAUAGCACCUGGAACUUCAACGGCACAUGGAAUCUGACCCAGAGCAA CGGCACCGAGGGCAAUGAUACAAUCACCCUGCCUUGCCGGAUCAAGCAGAUCAUCAACAUGUGG CAGGAAGUGGGCAAGGCCAUGUAUGCCCCUCCCAUCAGGGGACAGAUCAGGUGUAGCUCCAAUA UCACAGGCCUGAUCCUGACCCGGGACGGCGGAAAUAACCACAAUAACGAUACAGAGACAUUCAG GCCCGGCGGCGGCGACAUGAGGGAUAACUGGAGAUCCGAGCUGUACAAGUAUAAGGUGGUGAA GAUCGAGCCACUGGGAGUGGCACCAACCAAGUGCAAGAGGAGAGUGGUGCAGUCUCACAGCGG CUCCGGCGGCUCUGGCAGCGGCGGCCACGCAGCAGUGGGAACAAUCGGAGCAAUGAGCCUGGGC UUUCUGGGAGCAGCAGGCUCCACCAUGGGAGCAGCCUCUAUCACACUGACCGUGCAGGCAAGGC UGCUGCUGUCCGGCAUCGUGCAGCAGCAGAAUAACCUGCUGAGGGCACCAGAGCCUCAGCAGCA CCUGCUGCAGCUGACAGUGUGGGGCAUCAAGCAGCUGCAGGCCAGGGUGCUGGCAGUGGAGCA CUAUCUGAGGGACCAGCAGCUGCUGGGCAUCUGGGGCUGUAGCGGCAAGCUGAUCUGCUGUAC CGCCGUGCCCUGGAACGCCUCCUGGUCUAAUAAGACACUGGACAUGAUCUGGAAUAACAUGACC UGGAUGGAGUGGGAGCGCGAGAUCGAUAACUACACAGGCCUGAUCUAUACCCUGAUUGAGGAG UCACAGAACCAGCAGGAAAAGAACGAACAGGAACUGCUGGAACUGGAUUGAUAA (SEQ ID NO: 221) 001428_MD39_link14 (amino acid, dna, rna) MDWTWILFLVAAATRVHSVENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDP NPQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQVNATQGNTTQVN VTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNF DPIPIHYCTPAGYAILKCNNKTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTII VHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIK FTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQIINMWQEVGR AMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKR RVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQ QHLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWM QWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALD** (SEQ ID NO: 225) atggactggacttggattctgttcctggtggcagcagcaactagagtgcattccgtcgaaaacctgtgggtgaccgtgtattatggagt gcccgtgtggaaggaggcccggaccacactgttctgcgcctccgacgccaaggcctacgagacagaggtgcacaacgtgtgggcca cacacgcctgcgtgcctaccgatccaaatccccaggagatggtgctgggcaacgtgaccgagaactttaatatgtggaagaacgac atggtggatcagatgcacgaggacgtgatctctctgtgggcccagagcctgaagccttgcgtgaagctgaccccactgtgcgtgaca ctggagtgtacccaggtgaacgccacacagggcaataccacacaggtgaacgtgacccaagtgaatggcgacgagatgaagaact gttccttcaataccacaaccgagatccgggataagaagcagaaggcctacgccctgttttatagactggacctggtgcctctggagcg ggagaacagaggcgattctaatagcgcctccaagtatatcctgatcaactgcaatacatctgccatcacccaggcctgtcctaaagtg aatttcgatcctatcccaatccactactgcaccccagccggctatgccatcctgaagtgtaacaacaagaccttcaacggcaccggct cctgcaacaacgtgagcacagtgcagtgtacccacggcatcaagccagtggtgagcacccagctgctgctgaacggctccctggca gaggaggagatcatcatcaggtccgagaacctgacagacaatgtgaagaccatcatcgtgcacctggatcagtccgtggagatcgt gtgcacacggccaaacaataacaccgtgaagtctatcagaatcggccccggccagacattctactataccggcgacatcatcggca atatccgggaggcccactgtaacatctctgagaagaagtggcacgagatgctgcggagagtgagcgagaagctggccgagcacttc cccaataagacaatcaagtttaccagctcctctggcggcgatctggagatcacaacccacagcttcaactgcagaggcgagttctttt actgtaacaccagcggcctgtttaattccacatacatgcccaacggcacctatatgcctaatggcacaaataactctaacagcaccat catcctgccatgccggatcaagcagatcatcaatatgtggcaggaagtgggcagagccatgtatgcccctcccatcgccggcaacat cacatgtaacagcaatatcaccggcctgctgctggtgagggacggcggcaagaataacaatacagagatcttccgccccggcggcg gcgacatgagggataactggcgctccgagctgtacaagtataaggtggtggagatcaagccactgggagtggcaccaaccaggtgc aagaggcgcgtggtgggctcccactctggcagcggcggctccggctctggcggccacgcagcagtgggcctgggagccgtgagcct gggctttctgggagcagcaggctctaccatgggagcagccagcatcacactgaccgtgcaggcaaggcagctgctgtccggcatcgt gcagcagcagtctaacctgctgcaggcaccagagcctcagcagcacctgctgcaggacacacactggggcatcaagcagctgcag acccgcgtgctggccatcgagcactacctgaaggatcagcagctgctgggcatctggggctgctctggcaagctgatctgctgtaca gccgtgccttggaacagctcctggagcaataagtccctgacagacatctgggataatatgacctggatgcagtgggatagggaggtg agcaactacaccggcatcatctatcgcctgctggaagactcacagaatcagcaggaaaggaatgaacaggatctgctggcactgga ctgataa (SEQ ID NO: 226) AUGGACUGGACUUGGAUUCUGUUCCUGGUGGCAGCAGCAACUAGAGUGCAUUCCGUCGAAAAC CUGUGGGUGACCGUGUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCCGGACCACACUGUUCUG CGCCUCCGACGCCAAGGCCUACGAGACAGAGGUGCACAACGUGUGGGCCACACACGCCUGCGUG CCUACCGAUCCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGACCGAGAACUUUAAUAUGUGG AAGAACGACAUGGUGGAUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGCCCAGAGCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUACCCAGGUGAACGCCACACAGG GCAAUACCACACAGGUGAACGUGACCCAAGUGAAUGGCGACGAGAUGAAGAACUGUUCCUUCAA UACCACAACCGAGAUCCGGGAUAAGAAGCAGAAGGCCUACGCCCUGUUUUAUAGACUGGACCUG GUGCCUCUGGAGCGGGAGAACAGAGGCGAUUCUAAUAGCGCCUCCAAGUAUAUCCUGAUCAAC UGCAAUACAUCUGCCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGAUCCUAUCCCAAUCCACU ACUGCACCCCAGCCGGCUAUGCCAUCCUGAAGUGUAACAACAAGACCUUCAACGGCACCGGCUCC UGCAACAACGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCAGUGGUGAGCACCCAGCUGC UGCUGAACGGCUCCCUGGCAGAGGAGGAGAUCAUCAUCAGGUCCGAGAACCUGACAGACAAUGU GAAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGAGAUCGUGUGCACACGGCCAAACAAUAAC ACCGUGAAGUCUAUCAGAAUCGGCCCCGGCCAGACAUUCUACUAUACCGGCGACAUCAUCGGCA AUAUCCGGGAGGCCCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGAUGCUGCGGAGAGUGA GCGAGAAGCUGGCCGAGCACUUCCCCAAUAAGACAAUCAAGUUUACCAGCUCCUCUGGCGGCGA UCUGGAGAUCACAACCCACAGCUUCAACUGCAGAGGCGAGUUCUUUUACUGUAACACCAGCGGC CUGUUUAAUUCCACAUACAUGCCCAACGGCACCUAUAUGCCUAAUGGCACAAAUAACUCUAACA GCACCAUCAUCCUGCCAUGCCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAGUGGGCAGAGC CAUGUAUGCCCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCAAUAUCACCGGCCUGCUGCUG GUGAGGGACGGCGGCAAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGGCGGCGACAUGAGG GAUAACUGGCGCUCCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGAGUGGCA CCAACCAGGUGCAAGAGGCGCGUGGUGGGCUCCCACUCUGGCAGCGGCGGCUCCGGCUCUGGC GGCCACGCAGCAGUGGGCCUGGGAGCCGUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCUACC AUGGGAGCAGCCAGCAUCACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGGCAUCGUGCAGC AGCAGUCUAACCUGCUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCAGGACACACACUGGGG CAUCAAGCAGCUGCAGACCCGCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUG GGCAUCUGGGGCUGCUCUGGCAAGCUGAUCUGCUGUACAGCCGUGCCUUGGAACAGCUCCUGG AGCAAUAAGUCCCUGACAGACAUCUGGGAUAAUAUGACCUGGAUGCAGUGGGAUAGGGAGGUG AGCAACUACACCGGCAUCAUCUAUCGCCUGCUGGAAGACUCACAGAAUCAGCAGGAAAGGAAUG AACAGGAUCUGCUGGCACUGGACUGAUAA (SEQ ID NO: 227) 001428_MD39_link14_TS1 (amino acid, dna, rna) Repeat 1 optimized for human Repeat 2 optimized for human/mouse Repeat 3 optimized for mouse to prevent recombination and large repeats on the nucleic acid level MDWTWILFLVAAATRVHSVENLWVTVYYGVPVWKEARTTLFCASDAKAYETEVHNVWATHACVPTDP NPQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCVTLECTQVNATQGNTTQVN VTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNF DPIPIHYCTPAGYAILKCNNKTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTII VHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIK FTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSNSTIILPCRIKQIINMWQEVGR AMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKR RVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQ QHLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWM QWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALDGGVENLWVTVYYGVPVWKEARTTLFCASDAKAYE TEVHNVWATHACVPTDPNPQEMVLGNVTENFNMWKNDMVDQMHEDVISLWAQSLKPCVKLTPLCV TLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFYRLDLVPLERENRGDSNSAS KYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNKTFNGTGSCNNVSTVQCTHGIKPVVSTQLLLN GSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYTGDIIGNIREAHCNISEKKW HEMLRRVSEKLAEHFPNKTIKFTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNSTYMPNGTYMPNGTNNSN STIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNTEIFRPGGGDMRDNWRSE LYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLGFLGAAGSTMGAASITLTVQAR QLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRVLAIEHYLKDQQLLGIWGCSGKLICCTAVPWNS SWSNKSLTDIWDNMTWMQWDREVSNYTGIIYRLLEDSQNQQERNEQDLLALDGGVENLWVTVYYGVP VWKEARTTLFCASDAKAYETEVHNVWATHACVPTDPNPQEMVLGNVTENFNMWKNDMVDQMHED VISLWAQSLKPCVKLTPLCVTLECTQVNATQGNTTQVNVTQVNGDEMKNCSFNTTTEIRDKKQKAYALFY RLDLVPLERENRGDSNSASKYILINCNTSAITQACPKVNFDPIPIHYCTPAGYAILKCNNKTFNGTGSCNNVS TVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTDNVKTIIVHLDQSVEIVCTRPNNNTVKSIRIGPGQTFYYT GDIIGNIREAHCNISEKKWHEMLRRVSEKLAEHFPNKTIKFTSSSGGDLEITTHSFNCRGEFFYCNTSGLFNS TYMPNGTYMPNGTNNSNSTIILPCRIKQIINMWQEVGRAMYAPPIAGNITCNSNITGLLLVRDGGKNNNT EIFRPGGGDMRDNWRSELYKYKVVEIKPLGVAPTRCKRRVVGSHSGSGGSGSGGHAAVGLGAVSLGFLG AAGSTMGAASITLTVQARQLLSGIVQQQSNLLQAPEPQQHLLQDTHWGIKQLQTRVLAIEHYLKDQQLLG IWGCSGKLICCTAVPWNSSWSNKSLTDIWDNMTWMQWDREVSNYTGIIYRLLEDSQNQQERNEQDLL ALD** (SEQ ID NO: 228) ATGGACTGGACTTGGATTCTGTTCCTGGTGGCAGCAGCAACTAGAGTGCATTCCGTCGAAAACCTGT GGGTGACCGTGTATTATGGAGTGCCCGTGTGGAAGGAGGCCCGGACCACACTGTTCTGCGCCTCCG ACGCCAAGGCCTACGAGACAGAGGTGCACAACGTGTGGGCCACACACGCCTGCGTGCCTACCGATC CAAATCCCCAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTTAATATGTGGAAGAACGACATGG TGGATCAGATGCACGAGGACGTGATCTCTCTGTGGGCCCAGAGCCTGAAGCCTTGCGTGAAGCTGAC CCCACTGTGCGTGACACTGGAGTGTACCCAGGTGAACGCCACACAGGGCAATACCACACAGGTGAAC GTGACCCAAGTGAATGGCGACGAGATGAAGAACTGTTCCTTCAATACCACAACCGAGATCCGGGATA AGAAGCAGAAGGCCTACGCCCTGTTTTATAGACTGGACCTGGTGCCTCTGGAGCGGGAGAACAGAG GCGATTCTAATAGCGCCTCCAAGTATATCCTGATCAACTGCAATACATCTGCCATCACCCAGGCCTGTC CTAAAGTGAATTTCGATCCTATCCCAATCCACTACTGCACCCCAGCCGGCTATGCCATCCTGAAGTGTA ACAACAAGACCTTCAACGGCACCGGCTCCTGCAACAACGTGAGCACAGTGCAGTGTACCCACGGCAT CAAGCCAGTGGTGAGCACCCAGCTGCTGCTGAACGGCTCCCTGGCAGAGGAGGAGATCATCATCAG GTCCGAGAACCTGACAGACAATGTGAAGACCATCATCGTGCACCTGGATCAGTCCGTGGAGATCGTG TGCACACGGCCAAACAATAACACCGTGAAGTCTATCAGAATCGGCCCCGGCCAGACATTCTACTATAC CGGCGACATCATCGGCAATATCCGGGAGGCCCACTGTAACATCTCTGAGAAGAAGTGGCACGAGAT GCTGCGGAGAGTGAGCGAGAAGCTGGCCGAGCACTTCCCCAATAAGACAATCAAGTTTACCAGCTCC TCTGGCGGCGATCTGGAGATCACAACCCACAGCTTCAACTGCAGAGGCGAGTTCTTTTACTGTAACAC CAGCGGCCTGTTTAATTCCACATACATGCCCAACGGCACCTATATGCCTAATGGCACAAATAACTCTA ACAGCACCATCATCCTGCCATGCCGGATCAAGCAGATCATCAATATGTGGCAGGAAGTGGGCAGAGC CATGTATGCCCCTCCCATCGCCGGCAACATCACATGTAACAGCAATATCACCGGCCTGCTGCTGGTGA GGGACGGCGGCAAGAATAACAATACAGAGATCTTCCGCCCCGGCGGCGGCGACATGAGGGATAACT GGCGCTCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGCCACTGGGAGTGGCACCAACCAGGT GCAAGAGGCGCGTGGTGGGCTCCCACTCTGGCAGCGGCGGCTCCGGCTCTGGCGGCCACGCAGCA GTGGGCCTGGGAGCCGTGAGCCTGGGCTTTCTGGGAGCAGCAGGCTCTACCATGGGAGCAGCCAGC ATCACACTGACCGTGCAGGCAAGGCAGCTGCTGTCCGGCATCGTGCAGCAGCAGTCTAACCTGCTGC AGGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCATCAAGCAGCTGCAGACCC GCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCAGCTGCTGGGCATCTGGGGCTGCTCTGGCA AGCTGATCTGCTGTACAGCCGTGCCTTGGAACAGCTCCTGGAGCAATAAGTCCCTGACAGACATCTG GGATAATATGACCTGGATGCAGTGGGATAGGGAGGTGAGCAACTACACCGGCATCATCTATCGCCTG CTGGAAGACTCACAGAATCAGCAGGAAAGGAATGAACAGGATCTGCTGGCACTGGACGGGGGAGTC GAGAACCTCTGGGTCACCGTGTATTATGGAGTCCCCGTCTGGAAAGAAGCCCGAACCACCCTGTTTT GTGCCTCTGATGCTAAAGCCTACGAGACAGAGGTGCACAACGTGTGGGCTACACACGCTTGCGTGCC AACCGACCCAAACCCCCAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTCAACATGTGGAAGAA CGACATGGTGGATCAGATGCACGAGGATGTGATCTCTCTGTGGGCCCAGAGCCTGAAGCCTTGCGTG AAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGGTGAACGCTACACAGGGCAACACCACAC AGGTGAACGTGACCCAGGTGAACGGAGACGAGATGAAGAACTGTTCCTTCAACACCACAACCGAGA TCAGGGATAAGAAGCAGAAGGCCTACGCTCTGTTTTACAGACTGGACCTGGTGCCACTGGAGAGGG AGAACAGAGGCGATTCTAACAGCGCCTCCAAGTACATCCTGATCAACTGCAACACATCTGCCATCACC CAGGCTTGTCCTAAGGTGAACTTCGACCCTATCCCAATCCACTACTGCACACCAGCCGGCTACGCTAT CCTGAAGTGTAACAACAAGACCTTCAACGGAACCGGCTCCTGCAACAACGTGTCTACAGTGCAGTGT ACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCAGCCTGGCTGAGGAGGAG ATCATCATCCGGTCCGAGAACCTGACAGACAACGTGAAGACCATCATCGTGCACCTGGATCAGTCCG TGGAGATCGTGTGCACAAGGCCAAACAACAACACCGTGAAGTCTATCAGAATCGGACCCGGCCAGAC CTTCTACTACACCGGAGACATCATCGGCAACATCAGGGAGGCCCACTGTAACATCTCTGAGAAGAAG TGGCACGAGATGCTGAGGAGAGTGAGCGAGAAGCTGGCTGAGCACTTCCCTAACAAGACAATCAAG TTTACCAGCTCCTCTGGCGGAGATCTGGAGATCACAACCCACAGCTTCAACTGCAGAGGAGAGTTCTT TTACTGTAACACCAGCGGCCTGTTTAACTCCACATACATGCCCAACGGAACCTACATGCCTAACGGCA CAAACAACTCTAACAGCACCATCATCCTGCCCTGCAGGATCAAGCAGATCATCAACATGTGGCAGGAA GTGGGAAGAGCCATGTACGCTCCCCCTATCGCCGGCAACATCACATGTAACAGCAACATCACCGGAC TGCTGCTGGTGCGGGACGGCGGAAAGAACAACAACACAGAGATCTTCCGCCCTGGCGGAGGCGACA TGAGGGATAACTGGCGCTCCGAGCTGTACAAGTACAAGGTGGTGGAGATCAAGCCACTGGGAGTGG CTCCAACCAGGTGCAAGAGGAGGGTGGTGGGCAGCCACTCTGGCAGCGGAGGCTCCGGATCTGGA GGCCACGCTGCTGTGGGACTGGGAGCCGTGAGCCTGGGATTTCTGGGAGCTGCTGGATCTACCATG GGAGCTGCTAGCATCACACTGACCGTGCAGGCTAGGCAGCTGCTGTCCGGAATCGTGCAGCAGCAG TCTAACCTGCTGCAGGCTCCCGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGGGCATCAAGC AGCTGCAGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCAGCTGCTGGGCATCTGGG GATGTTCTGGCAAGCTGATCTGCTGTACAGCTGTGCCATGGAACAGCTCCTGGAGCAACAAGTCCCT GACAGACATCTGGGATAACATGACCTGGATGCAGTGGGATCGGGAGGTGAGCAACTACACCGGCAT CATCTACCGCCTGCTGGAAGACTCACAGAATCAGCAGGAACGGAATGAACAGGACCTCCTCGCACTG GATGGCGGAGTCGAAAACCTGTGGGTCACCGTCTACTATGGAGTGCCAGTGTGGAAAGAGGCTAGG ACTACCCTGTTCTGTGCCAGCGATGCCAAAGCCTACGAGACAGAGGTGCACAACGTGTGGGCAACAC ACGCATGCGTGCCAACCGACCCAAATCCCCAGGAGATGGTGCTGGGCAACGTGACCGAGAACTTCAA TATGTGGAAGAACGACATGGTGGATCAGATGCACGAGGATGTGATCTCTCTGTGGGCCCAGAGCCT GAAGCCTTGCGTGAAGCTGACCCCACTGTGCGTGACACTGGAGTGTACCCAGGTGAACGCCACACAG GGCAATACCACACAGGTGAACGTGACCCAAGTGAATGGCGACGAGATGAAGAACTGTTCCTTCAATA CCACAACCGAGATCAGGGATAAGAAGCAGAAGGCCTACGCCCTGTTTTATAGACTGGACCTGGTGCC ACTGGAGAGGGAGAACAGAGGCGATTCTAATAGCGCCTCCAAGTATATCCTGATCAACTGCAATACA TCTGCCATCACCCAGGCCTGTCCTAAAGTGAATTTCGACCCTATCCCAATCCACTACTGCACACCAGCC GGCTATGCCATCCTGAAGTGTAACAACAAGACCTTCAACGGCACCGGCTCCTGCAACAACGTGAGCA CAGTGCAGTGTACCCACGGCATCAAGCCCGTGGTGAGCACCCAGCTGCTGCTGAACGGCTCCCTGGC AGAGGAGGAGATCATCATCCGGTCCGAGAACCTGACAGACAATGTGAAGACCATCATCGTGCACCTG GATCAGTCCGTGGAGATCGTGTGCACAAGGCCAAACAATAACACCGTGAAGTCTATCAGAATCGGCC CCGGCCAGACCTTCTACTATACCGGCGACATCATCGGCAATATCAGGGAGGCCCACTGTAACATCTCT GAGAAGAAGTGGCACGAGATGCTGAGGAGAGTGAGCGAGAAGCTGGCCGAGCACTTCCCTAATAA GACAATCAAGTTTACCAGCTCCTCTGGCGGCGATCTGGAGATCACAACCCACAGCTTCAACTGCAGA GGCGAGTTCTTTTACTGTAACACCAGCGGCCTGTTTAATTCCACATACATGCCCAACGGCACCTATAT GCCTAATGGCACAAATAACTCTAACAGCACCATCATCCTGCCCTGCAGGATCAAGCAGATCATCAATA TGTGGCAGGAAGTGGGCAGAGCCATGTATGCCCCTCCCATCGCCGGCAACATCACATGTAACAGCAA TATCACCGGCCTGCTGCTGGTGCGGGACGGCGGCAAGAATAACAATACAGAGATCTTCCGCCCCGGC GGCGGCGACATGAGGGATAACTGGCGCTCCGAGCTGTACAAGTATAAGGTGGTGGAGATCAAGCCA CTGGGAGTGGCACCAACCAGGTGCAAGAGGCGCGTGGTGGGCTCCCACTCTGGCAGCGGCGGCTCC GGCTCTGGCGGCCACGCAGCAGTGGGCCTGGGAGCCGTGTCCCTGGGCTTTCTGGGAGCAGCAGGC TCTACCATGGGAGCAGCCAGCATCACACTGACCGTGCAGGCAAGGCAGCTGCTGTCCGGCATCGTGC AGCAGCAGTCTAACCTGCTGCAGGCACCAGAGCCTCAGCAGCACCTGCTGCAGGACACACACTGGG GCATCAAGCAGCTGCAGACCCGCGTGCTGGCCATCGAGCACTACCTGAAGGATCAGCAGCTGCTGG GCATCTGGGGCTGTTCTGGCAAGCTGATCTGCTGTACAGCCGTGCCATGGAACAGCTCCTGGAGCAA TAAGTCCCTGACAGACATCTGGGATAATATGACCTGGATGCAGTGGGATCGGGAGGTGAGCAACTAC ACCGGCATCATCTATCGCCTGCTGGAGGACTCACAGAATCAGCAGGAGCGGAACGAACAGGATCTG CTGGCACTGGATTGATAA (SEQ ID NO: 226) AUGGACUGGACUUGGAUUCUGUUCCUGGUGGCAGCAGCAACUAGAGUGCAUUCCGUCGAAAAC CUGUGGGUGACCGUGUAUUAUGGAGUGCCCGUGUGGAAGGAGGCCCGGACCACACUGUUCUG CGCCUCCGACGCCAAGGCCUACGAGACAGAGGUGCACAACGUGUGGGCCACACACGCCUGCGUG CCUACCGAUCCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGACCGAGAACUUUAAUAUGUGG AAGAACGACAUGGUGGAUCAGAUGCACGAGGACGUGAUCUCUCUGUGGGCCCAGAGCCUGAAG CCUUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUACCCAGGUGAACGCCACACAGG GCAAUACCACACAGGUGAACGUGACCCAAGUGAAUGGCGACGAGAUGAAGAACUGUUCCUUCAA UACCACAACCGAGAUCCGGGAUAAGAAGCAGAAGGCCUACGCCCUGUUUUAUAGACUGGACCUG GUGCCUCUGGAGCGGGAGAACAGAGGCGAUUCUAAUAGCGCCUCCAAGUAUAUCCUGAUCAAC UGCAAUACAUCUGCCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGAUCCUAUCCCAAUCCACU ACUGCACCCCAGCCGGCUAUGCCAUCCUGAAGUGUAACAACAAGACCUUCAACGGCACCGGCUCC UGCAACAACGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCAGUGGUGAGCACCCAGCUGC UGCUGAACGGCUCCCUGGCAGAGGAGGAGAUCAUCAUCAGGUCCGAGAACCUGACAGACAAUGU GAAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGAGAUCGUGUGCACACGGCCAAACAAUAAC ACCGUGAAGUCUAUCAGAAUCGGCCCCGGCCAGACAUUCUACUAUACCGGCGACAUCAUCGGCA AUAUCCGGGAGGCCCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGAUGCUGCGGAGAGUGA GCGAGAAGCUGGCCGAGCACUUCCCCAAUAAGACAAUCAAGUUUACCAGCUCCUCUGGCGGCGA UCUGGAGAUCACAACCCACAGCUUCAACUGCAGAGGCGAGUUCUUUUACUGUAACACCAGCGGC CUGUUUAAUUCCACAUACAUGCCCAACGGCACCUAUAUGCCUAAUGGCACAAAUAACUCUAACA GCACCAUCAUCCUGCCAUGCCGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAGUGGGCAGAGC CAUGUAUGCCCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCAAUAUCACCGGCCUGCUGCUG GUGAGGGACGGCGGCAAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGGCGGCGACAUGAGG GAUAACUGGCGCUCCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAGCCACUGGGAGUGGCA CCAACCAGGUGCAAGAGGCGCGUGGUGGGCUCCCACUCUGGCAGCGGCGGCUCCGGCUCUGGC GGCCACGCAGCAGUGGGCCUGGGAGCCGUGAGCCUGGGCUUUCUGGGAGCAGCAGGCUCUACC AUGGGAGCAGCCAGCAUCACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGGCAUCGUGCAGC AGCAGUCUAACCUGCUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCAGGACACACACUGGGG CAUCAAGCAGCUGCAGACCCGCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUG GGCAUCUGGGGCUGCUCUGGCAAGCUGAUCUGCUGUACAGCCGUGCCUUGGAACAGCUCCUGG AGCAAUAAGUCCCUGACAGACAUCUGGGAUAAUAUGACCUGGAUGCAGUGGGAUAGGGAGGUG AGCAACUACACCGGCAUCAUCUAUCGCCUGCUGGAAGACUCACAGAAUCAGCAGGAAAGGAAUG AACAGGAUCUGCUGGCACUGGACGGGGGAGUCGAGAACCUCUGGGUCACCGUGUAUUAUGGAG UCCCCGUCUGGAAAGAAGCCCGAACCACCCUGUUUUGUGCCUCUGAUGCUAAAGCCUACGAGAC AGAGGUGCACAACGUGUGGGCUACACACGCUUGCGUGCCAACCGACCCAAACCCCCAGGAGAUG GUGCUGGGCAACGUGACCGAGAACUUCAACAUGUGGAAGAACGACAUGGUGGAUCAGAUGCAC GAGGAUGUGAUCUCUCUGUGGGCCCAGAGCCUGAAGCCUUGCGUGAAGCUGACCCCACUGUGC GUGACACUGGAGUGUACCCAGGUGAACGCUACACAGGGCAACACCACACAGGUGAACGUGACCC AGGUGAACGGAGACGAGAUGAAGAACUGUUCCUUCAACACCACAACCGAGAUCAGGGAUAAGAA GCAGAAGGCCUACGCUCUGUUUUACAGACUGGACCUGGUGCCACUGGAGAGGGAGAACAGAGG CGAUUCUAACAGCGCCUCCAAGUACAUCCUGAUCAACUGCAACACAUCUGCCAUCACCCAGGCUU GUCCUAAGGUGAACUUCGACCCUAUCCCAAUCCACUACUGCACACCAGCCGGCUACGCUAUCCU GAAGUGUAACAACAAGACCUUCAACGGAACCGGCUCCUGCAACAACGUGUCUACAGUGCAGUGU ACCCACGGCAUCAAGCCCGUGGUGAGCACCCAGCUGCUGCUGAACGGCAGCCUGGCUGAGGAGG AGAUCAUCAUCCGGUCCGAGAACCUGACAGACAACGUGAAGACCAUCAUCGUGCACCUGGAUCA GUCCGUGGAGAUCGUGUGCACAAGGCCAAACAACAACACCGUGAAGUCUAUCAGAAUCGGACCC GGCCAGACCUUCUACUACACCGGAGACAUCAUCGGCAACAUCAGGGAGGCCCACUGUAACAUCU CUGAGAAGAAGUGGCACGAGAUGCUGAGGAGAGUGAGCGAGAAGCUGGCUGAGCACUUCCCUA ACAAGACAAUCAAGUUUACCAGCUCCUCUGGCGGAGAUCUGGAGAUCACAACCCACAGCUUCAA CUGCAGAGGAGAGUUCUUUUACUGUAACACCAGCGGCCUGUUUAACUCCACAUACAUGCCCAAC GGAACCUACAUGCCUAACGGCACAAACAACUCUAACAGCACCAUCAUCCUGCCCUGCAGGAUCAA GCAGAUCAUCAACAUGUGGCAGGAAGUGGGAAGAGCCAUGUACGCUCCCCCUAUCGCCGGCAAC AUCACAUGUAACAGCAACAUCACCGGACUGCUGCUGGUGCGGGACGGCGGAAAGAACAACAACA CAGAGAUCUUCCGCCCUGGCGGAGGCGACAUGAGGGAUAACUGGCGCUCCGAGCUGUACAAGU ACAAGGUGGUGGAGAUCAAGCCACUGGGAGUGGCUCCAACCAGGUGCAAGAGGAGGGUGGUGG GCAGCCACUCUGGCAGCGGAGGCUCCGGAUCUGGAGGCCACGCUGCUGUGGGACUGGGAGCCG UGAGCCUGGGAUUUCUGGGAGCUGCUGGAUCUACCAUGGGAGCUGCUAGCAUCACACUGACCG UGCAGGCUAGGCAGCUGCUGUCCGGAAUCGUGCAGCAGCAGUCUAACCUGCUGCAGGCUCCCG AGCCUCAGCAGCACCUGCUGCAGGACACACACUGGGGCAUCAAGCAGCUGCAGACCCGCGUGCU GGCCAUCGAGCACUACCUGAAGGAUCAGCAGCUGCUGGGCAUCUGGGGAUGUUCUGGCAAGCU GAUCUGCUGUACAGCUGUGCCAUGGAACAGCUCCUGGAGCAACAAGUCCCUGACAGACAUCUGG GAUAACAUGACCUGGAUGCAGUGGGAUCGGGAGGUGAGCAACUACACCGGCAUCAUCUACCGCC UGCUGGAAGACUCACAGAAUCAGCAGGAACGGAAUGAACAGGACCUCCUCGCACUGGAUGGCGG AGUCGAAAACCUGUGGGUCACCGUCUACUAUGGAGUGCCAGUGUGGAAAGAGGCUAGGACUAC CCUGUUCUGUGCCAGCGAUGCCAAAGCCUACGAGACAGAGGUGCACAACGUGUGGGCAACACAC GCAUGCGUGCCAACCGACCCAAAUCCCCAGGAGAUGGUGCUGGGCAACGUGACCGAGAACUUCA AUAUGUGGAAGAACGACAUGGUGGAUCAGAUGCACGAGGAUGUGAUCUCUCUGUGGGCCCAGA GCCUGAAGCCUUGCGUGAAGCUGACCCCACUGUGCGUGACACUGGAGUGUACCCAGGUGAACG CCACACAGGGCAAUACCACACAGGUGAACGUGACCCAAGUGAAUGGCGACGAGAUGAAGAACUG UUCCUUCAAUACCACAACCGAGAUCAGGGAUAAGAAGCAGAAGGCCUACGCCCUGUUUUAUAGA CUGGACCUGGUGCCACUGGAGAGGGAGAACAGAGGCGAUUCUAAUAGCGCCUCCAAGUAUAUC CUGAUCAACUGCAAUACAUCUGCCAUCACCCAGGCCUGUCCUAAAGUGAAUUUCGACCCUAUCC CAAUCCACUACUGCACACCAGCCGGCUAUGCCAUCCUGAAGUGUAACAACAAGACCUUCAACGGC ACCGGCUCCUGCAACAACGUGAGCACAGUGCAGUGUACCCACGGCAUCAAGCCCGUGGUGAGCA CCCAGCUGCUGCUGAACGGCUCCCUGGCAGAGGAGGAGAUCAUCAUCCGGUCCGAGAACCUGAC AGACAAUGUGAAGACCAUCAUCGUGCACCUGGAUCAGUCCGUGGAGAUCGUGUGCACAAGGCC AAACAAUAACACCGUGAAGUCUAUCAGAAUCGGCCCCGGCCAGACCUUCUACUAUACCGGCGACA UCAUCGGCAAUAUCAGGGAGGCCCACUGUAACAUCUCUGAGAAGAAGUGGCACGAGAUGCUGA GGAGAGUGAGCGAGAAGCUGGCCGAGCACUUCCCUAAUAAGACAAUCAAGUUUACCAGCUCCUC UGGCGGCGAUCUGGAGAUCACAACCCACAGCUUCAACUGCAGAGGCGAGUUCUUUUACUGUAA CACCAGCGGCCUGUUUAAUUCCACAUACAUGCCCAACGGCACCUAUAUGCCUAAUGGCACAAAU AACUCUAACAGCACCAUCAUCCUGCCCUGCAGGAUCAAGCAGAUCAUCAAUAUGUGGCAGGAAG UGGGCAGAGCCAUGUAUGCCCCUCCCAUCGCCGGCAACAUCACAUGUAACAGCAAUAUCACCGG CCUGCUGCUGGUGCGGGACGGCGGCAAGAAUAACAAUACAGAGAUCUUCCGCCCCGGCGGCGGC GACAUGAGGGAUAACUGGCGCUCCGAGCUGUACAAGUAUAAGGUGGUGGAGAUCAAGCCACUG GGAGUGGCACCAACCAGGUGCAAGAGGCGCGUGGUGGGCUCCCACUCUGGCAGCGGCGGCUCC GGCUCUGGCGGCCACGCAGCAGUGGGCCUGGGAGCCGUGUCCCUGGGCUUUCUGGGAGCAGCA GGCUCUACCAUGGGAGCAGCCAGCAUCACACUGACCGUGCAGGCAAGGCAGCUGCUGUCCGGCA UCGUGCAGCAGCAGUCUAACCUGCUGCAGGCACCAGAGCCUCAGCAGCACCUGCUGCAGGACAC ACACUGGGGCAUCAAGCAGCUGCAGACCCGCGUGCUGGCCAUCGAGCACUACCUGAAGGAUCAG CAGCUGCUGGGCAUCUGGGGCUGUUCUGGCAAGCUGAUCUGCUGUACAGCCGUGCCAUGGAAC AGCUCCUGGAGCAAUAAGUCCCUGACAGACAUCUGGGAUAAUAUGACCUGGAUGCAGUGGGAU CGGGAGGUGAGCAACUACACCGGCAUCAUCUAUCGCCUGCUGGAGGACUCACAGAAUCAGCAGG AGCGGAACGAACAGGAUCUGCUGGCACUGGAUUGAUAA (SEQ ID NO: 227) 

1. A composition comprising an expressible nucleic acid sequence comprising: (i) a first nucleic acid sequence encoding a soluble retroviral trimer or a soluble monomer of a retroviral trimer or a pharmaceutically acceptable salt thereof.
 2. The composition of claim 1, wherein the composition further comprises: a regulatory sequence operably linked to the first nucleotide sequence, wherein the first nucleic acid sequence comprises at least about 70% sequence identity to a nucleotide sequence encoding a soluble trimer of human immunodeficiency virus-1 (HIV-1) ENV or a soluble monomer of HIV-1 ENV.
 3. (canceled)
 4. The composition of claim 1, wherein the expressible nucleic acid sequence comprises the expressible nucleic acid sequence comprising: (i) one or a combination of nucleic acid sequences chosen from: SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 130, SEQ ID NO: 131; and/or (ii) one or a combination of nucleic acid sequences wherein the at least one nucleic acid sequence comprises at least about 70% sequence identity to a sequence identified as including: AD8, CPG9.2, 001428, TR011, X2278, 398F1, 246F3, CE0217, CE1176, 25710, BJOX2000, CH119, X1632, CNE8, CNE55, or 001428; and/or (iii) one or a combination of nucleic acid sequences that encode an amino acid sequence chosen from: SEQ ID NO: 55, SEQ ID NO: 58, SEQ ID NO: 61, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 64, SEQ ID NO: 80, SEQ ID NO: 83, SEQ ID NO: 86, SEQ ID NO: 89, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID NO: 114, SEQ ID NO: 117, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 93, SEQ ID NO: 126, SEQ ID NO: 129, SEQ ID NO: 132; and/or (iv) one or a combination of nucleic acid sequences that encode at least one amino acid sequences comprising at least about 70% sequence identity to a sequence identified as including: AD8, CPG9.2, 001428, TR011, X2278, 398F1, 246F3, CE0217, CE1176, 25710, BJOX2000, CH119, X1632, CNE8, CNE55, or
 001428. 5.-8. (canceled)
 9. The composition of claim 1, wherein the expressible nucleic acid sequence further comprises a nucleic acid sequence that encodes a viral antigen comprises at least about 70% sequence identity to SEQ ID NO: 4 or a pharmaceutically acceptable salt thereof.
 10. The composition of claim 1, wherein the expressible nucleic acid sequence further comprises at least two non-contiguous nucleic acid sequences comprising at least about 70% sequence identity to a leader sequence and further comprising a sequence encoding a linker positioned between the two non-contiguous nucleic acid sequences. 11-12. (canceled)
 13. The composition of claim 1, wherein the first nucleotide sequence encodes at least three HIV antigens, each HIV antigen expressed as a contiguous polypeptide chain that is secreted by a cell upon expression.
 14. The composition of claim 1, wherein the first nucleic acid sequence encodes a self-assembling polypeptide comprises at least about 70% sequence identity to SEQ ID NO: 2 or a pharmaceutically acceptable salt thereof.
 15. The composition of claim 1 further comprising a nucleic acid molecule that is a DNA plasmid; wherein the plasmid comprises an expressible nucleic acid sequence comprising at least one nucleic acid or combination thereof that is or encodes a nucleic acid or amino acid comprising at least about 70% sequence identity to an amino acid sequence chosen from: SEQ ID NO: 133 through SEQ ID NO: 153, or a pharmaceutically acceptable salt thereof.
 16. A pharmaceutical composition comprising: (i) the composition of claim 1; and (ii) a pharmaceutically acceptable carrier. 17-19. (canceled)
 20. A method of vaccinating a subject comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to the subject.
 21. The method of claim 20, wherein the administering is accomplished by oral administration, parenteral administration, sublingual administration, transdermal administration, rectal administration, transmucosal administration; topical administration, inhalation, buccal administration, intrapleural administration, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration intramuscular administration, intranasal administration, intrathecal administration, and intraarticular administration, or combinations thereof.
 21. The method of claim 20, wherein the therapeutically effective dose is from about 1 to about 30 micrograms of expressible nucleic acid sequence.
 22. The method of claim 20, wherein the method is free of activating any mannose-binding lectin or complement process.
 23. The method of claim 20, wherein the subject is a human.
 24. (canceled)
 25. A method of inducing an immune response in a subject comprising administering to the subject the pharmaceutical composition of claim
 16. 26.-33. (canceled)
 34. A method of neutralizing one or plurality of viruses in a subject comprising administering to the subject the pharmaceutical composition of claim
 16. 35-39. (canceled)
 40. A method of stimulating a therapeutically effective antigen-specific immune response against a virus in a mammal infected with the virus comprising administering the pharmaceutical composition of claim
 16. 41. The method of claim 40, wherein the method is free of activating any mannose-binding lectin or complement pathway associated with an immune response. 42-43. (canceled)
 44. A vaccine comprising an expressible nucleotide sequence comprising: (i) one or a combination of nucleic acid sequences chosen from: SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, and SEQ ID NO: 72; and/or (ii) one or a combination of nucleic acid sequences wherein the at least one nucleic acid sequence comprises at least about 70% sequence identity to a sequence chosen from: SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, and SEQ ID NO: 72; and/or (iii) one or a combination of nucleic acid sequences that encode an amino acid sequence chosen from: SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; SEQ ID NO: 58, SEQ ID NO: 59; or SEQ ID NO: 60; and/or (iv) one or a combination of nucleic acid sequences that encode at least one amino acid sequences comprising at least about 70% sequence identity to a sequence chosen from: SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; SEQ ID NO: 58, SEQ ID NO: 59; or SEQ ID NO:
 60. 45. The vaccine of claim 44 further comprising a linker fusing the three expressible noncontiguous nucleic acid sequences.
 46. The vaccine of claim 45, wherein the linker is an amino acid sequence comprising at least about 70% sequence identity to SEQ ID NO:
 8. 47-57. (canceled) 